NCBI Conserved Domain Search

alphacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...

1495-1781

9.60e-134

alphacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) found in non-structural protein 3 (Nsp3) of alphacoronavirus, including Swine acute diarrhea syndrome coronavirus (SADS-CoV) which causes severe diarrhea in piglets, and Human coronavirus 229E which infects humans and bats and causes the common cold. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. PLPro is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. PLPro, which belongs to the MEROPS peptidase C16 family, participates in the proteolytic processing of the N-terminal region of the replicase polyprotein; it can cleave Nsp1|Nsp2, Nsp2|Nsp3, and Nsp3|Nsp4 sites and its activity is dependent on zinc. Besides cleaving the polyproteins, PLPro also possesses a related enzymatic activity to promote virus replication: deubiquitinating (DUB) and de-ISGylating activities. Both, ubiquitin (Ub) and Ub-like interferon-stimulated gene product 15 (ISG15), are involved in preventing viral infection; coronaviruses utilize Ubl-conjugating pathways to counter the pro-inflammatory properties of Ubl-conjugated host proteins via the action of PLPro, which processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. The Nsp3 PLPro domain in SADS-CoV and many others has also been shown to antagonize host innate immune induction of type I interferon by interacting with IRF3 and blocking its activation.

Pssm-ID: 409648 Cd Length: 289 Bit Score: 421.26 E-value: 9.60e-134

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1495 GTIPVKVTEDTVNQKRVSVALDKTYGEQLkGTVVIKDKDVTNQ-LPSVSDAGEKVvkALDVDWNAYYGFPNAAAFSASSH 1573
Cdd:cd21731     1 KSVVVKVTEDGRNVKDVVVDTDKTFGEQL-GVCSVNDKDVTGVvPPDDSDKVVSV--APDVDWDSHYGFPNAAVFHTLDH 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1574 DAYKFDVVTHNNFIVHKQTDNNCWVNAICLALQRLKPTWKFPGVKSLWDVFLTRKTAGFVHMLYHISGLKKGQPGDAELT 1653
Cdd:cd21731    78 SAYAFESDIVNGKRVLKQSDNNCWVNAVCLQLQFAKPTFKSEGLQALWNKFLTGDVAGFVHWLYWITGANKGDPGDAENT 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1654 LHKLGELMVSDSIVTITHTTACDKCAKIENFTGPVV-AAPLMIYGTDETCVHGVSVNVKVTSIRGTVAITSLIGPVVGDV 1732
Cdd:cd21731   158 LNKLSKYLVSSGSVTVERTTGCDSCNSKRTVTTPVVnASVLRSGVDDGVCKHGVKVTTRVVSVKGTVIITSVGKPVVSDA 237

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 240015189 1733 ---IDATGYICYTGLNSRGHYTYYDNRNGLMVDAEKAYHFEKNLLQVTTAIA 1781
Cdd:cd21731   238 lllLDGVSYTAFSGDVDNGHYTVYDKATGKVYDGDKTVSFKLDLLSVTSVVV 289

alphaCoV_Nsp8

cd21830

alphacoronavirus non-structural protein 8; This model represents the non-structural protein 8 ...

3575-3769

2.24e-126

alphacoronavirus non-structural protein 8; This model represents the non-structural protein 8 (Nsp8) region of alphacoronaviruses that include Feline infectious peritonitis virus (FCoV), Human coronavirus NL63 (HCoV-NL63), and Porcine epidemic diarrhea coronavirus (PEDV), among others. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9, and Nsp10 form functional complexes with CoV core enzymes and thereby stimulate replication. Most importantly, a complex of Nsp8 with Nsp7 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the genes encoding Nsp8 and Nsp7 have been shown to delay virus growth. Nsp8 and Nsp7 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp8 with Nsp7 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp8 has a novel 'golf-club' fold composed of an N-terminal 'shaft' domain and a C-terminal 'head' domain. The shaft domain contains three helices, one of which is very long, while the head domain contains another three helices and seven beta-strands, forming an alpha/beta fold. FCoV Nsp8 forms a 1:2 heterotrimer with Nsp7; the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to the template length.

Pssm-ID: 409257 Cd Length: 195 Bit Score: 395.95 E-value: 2.24e-126

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3575 SVASAYAALPSWIAYEKARADLEEAKKNDVSPQLLKQLTKACNIAKSEFEREVSVQKKLDKMAEQAAASMYKEARAVDRK 3654
Cdd:cd21830     1 SVASTFANMPSFIAYETARQDYEDAVKNGSSPQLIKQLKKAMNIAKSEFDREASVQRKLDRMAEQAAAQMYKEARAVNRK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3655 SKIVSAMHSLLFGMLKKLDMSSVNTIIEQARNGVLPLSIIPAASATRLIVVTPNLEVLSKVRQENNVHYAGAIWSIVEVK 3734
Cdd:cd21830    81 SKVISAMHSLLFGMLRRLDMSSVDTILNLAKDGVVPLSIIPAASATRLVVVVPDLESFSKIRRDGCVHYAGVVWTIVDIK 160

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 240015189 3735 DANGSQVHLKEVTAANELNITWPLSITCERTTKLQ 3769
Cdd:cd21830   161 DNDGKVVHLKEVTAANEESLAWPLHLNCERIVKLQ 195

alpha_betaCoV_Nsp10

cd21901

alphacoronavirus and betacoronavirus non-structural protein 10; This model represents the ...

3881-4010

5.81e-93

alphacoronavirus and betacoronavirus non-structural protein 10; This model represents the non-structural protein 10 (Nsp10) of alpha- and betacoronaviruses, including highly pathogenic betacoronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), Middle East respiratory syndrome-related (MERS) CoV, and alphacoronaviruses such as Human coronavirus 229E. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9, and Nsp10 form functional complexes with CoV core enzymes and thereby stimulate replication. Coronaviruses cap their mRNAs; RNA cap methylation may involve at least three proteins: Nsp10, Nsp14, and Nsp16. Nsp10 serves as a cofactor for both Nsp14 and Nsp16. Nsp14 consists of 2 domains with different enzymatic activities: an N-terminal ExoN domain and a C-terminal cap (guanine-N7) methyltransferase (N7-MTase) domain. The association of Nsp10 with Nsp14 enhances Nsp14's exoribonuclease (ExoN) activity, and not its N7-Mtase activity. ExoN is important for proofreading and therefore, the prevention of lethal mutations. The Nsp10/Nsp14 complex hydrolyzes double-stranded RNA in a 3' to 5' direction as well as a single mismatched nucleotide at the 3'-end, mimicking an erroneous replication product, and may function in a replicative mismatch repair mechanism. Nsp16 Cap-0 specific (nucleoside-2'-O-)-methyltransferase (2'OMTase) acts sequentially to Nsp14 MTase in RNA capping methylation, and methylates the RNA cap at the ribose 2'-O position; it catalyzes the conversion of the cap-0 structure on m7GpppA-RNA to a cap-1 structure. The association of Nsp10 with Nsp16 enhances Nsp16's 2'OMTase activity, possibly through enhanced RNA binding affinity. Additionally, transmissible gastroenteritis virus (TGEV) Nsp10, Nsp16 and their complex can interact with DII4, which normally binds to Notch receptors; this interaction may disturb Notch signaling. Nsp10 also binds 2 zinc ions with high affinity.

Pssm-ID: 409326 Cd Length: 130 Bit Score: 297.27 E-value: 5.81e-93

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3881 AGKPTEHPSNSGLLTLCAFAPDPAKAYVDAVKRGMQPVTNCVKMLSNGAGNGMAVTNGVESNTQQDSYGGASVCIYCRCH 3960
Cdd:cd21901     1 AGKQTEVASNSSLLTLCAFAVDPAKTYLDAVKSGGKPVGNCVKMLTNGTGTGQAITVKPEANTNQDSYGGASVCLYCRAH 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 240015189 3961 VEHPAIDGLCRFKGKFVQVPTGTQDPIRFCIENEICVVCGCWLNNGCMCD 4010
Cdd:cd21901    81 VEHPDMDGVCKLKGKYVQVPLGTNDPVRFCLENDVCKVCGCWLGNGCSCD 130

TGEV-like_alphaCoV_Nsp1

cd21687

non-structural protein 1 from transmissible gastroenteritis virus and similar ...

2-105

2.72e-69

non-structural protein 1 from transmissible gastroenteritis virus and similar alphacoronaviruses; This model represents the non-structural protein 1 (Nsp1) from transmissible gastroenteritis virus (TGEV) and similar alphacoronaviruses from the tegacovirus and minacovirus subgenera. CoVs utilize a multi-subunit replication/transcription machinery assembled from a set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins. Nsp1 is the N-terminal cleavage product released from the ORF1a polyprotein by the action of papain-like protease (PLpro). Though Nsp1s of alphaCoVs and betaCoVs share structural similarity, they show no significant sequence similarity and may be considered as genus-specific markers. Despite low sequence similarity, the Nsp1s of alphaCoVs and betaCoVs exhibit remarkably similar biological functions, and are involved in the regulation of both host and viral gene expression. CoV Nsp1 induces suppression of host gene expression and interferes with host immune response. It inhibits host gene expression in two ways: by targeting the translation and stability of cellular mRNAs, and by inhibiting mRNA translation and inducing an endonucleolytic RNA cleavage in the 5'-UTR of cellular mRNAs through its tight association with the 40S ribosomal subunit, a key component of the cellular translation machinery. Inhibition of host mRNA translation includes that of type I interferons, major components of the host innate immune response. Nsp1 is critical in regulating viral replication and gene expression, as shown by multiple evidences, including: mutations in the Nsp1 coding region of the TGEV and murine hepatitis virus (MHV) genomes cause drastic reduction or elimination of infectious virus; bovine coronavirus (BCoV) Nsp1 is an RNA-binding protein that interacts with cis-acting replication elements in the 5'-UTR of the BCoV genome, implying its potential role in the regulation of viral translation or replication; and SARS-CoV Nsp1 enhances virus replication by binding to a stem-loop structure in the 5'-UTR of its genome.

Pssm-ID: 439284 Cd Length: 104 Bit Score: 228.52 E-value: 2.72e-69

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189    2 SSKHFKILVNEDYQVNVPSLPFRDVSQEIKYCYRNGFDGYVFVPEYRRDLVDCNRKDHYVIGVLGNGISDLKPVLLTEPS 81
Cdd:cd21687     1 SSKQFKILVNEDYQVNVPSLPFRDVLQEIKYCYRNGFDGYVFVPEYRRDLVDCDRKDHYVIGVLGNGISDLKPVLLTEPS 80

                          90       100
                  ....*....|....*....|....
gi 240015189   82 VMLQGFIVRANCNGVLEDFDLKIA 105
Cdd:cd21687    81 VMLQGFIVRANCNGVLEDFDLKIA 104

alphaCoV_Nsp9

cd21897

alphacoronavirus non-structural protein 9; This model represents the non-structural protein 9 ...

3770-3880

1.02e-64

alphacoronavirus non-structural protein 9; This model represents the non-structural protein 9 (Nsp9) of alphacoronaviruses, including Porcine epidemic diarrhea virus (PEDV), Porcine transmissible gastroenteritis coronavirus (TGEV), and Human coronavirus 229E. CoVs utilize a multi-subunit replication/transcription machinery assembled from a set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins. All of these Nsps, except for Nsp1 and Nsp2, are considered essential for transcription, replication, and translation of the viral RNA. Nsp9, with Nsp7, Nsp8, and Nsp10, localizes within the replication complex. Nsp9 is an essential single-stranded RNA-binding protein for coronavirus replication; it shares structural similarity to the oligosaccharide-binding (OB) fold, which is characteristic of proteins that bind to ssDNA or ssRNA. Nsp9 requires dimerization for binding and orienting RNA for subsequent use by the replicase machinery. CoV Nsp9s have diverse forms of dimerization that promote their biological function, which may help elucidate the mechanism underlying CoVs replication and contribute to the development of antiviral drugs. Generally, dimers are formed via interaction of the parallel alpha-helices containing the protein-protein interaction motif GXXXG; additionally, the N-finger region may also play a critical role in dimerization as seen in porcine delta coronavirus (PDCoV) Nsp9. As a member of the replication complex, Nsp9 may not have a specific RNA-binding sequence but may act in conjunction with other Nsps as a processivity factor, as shown by mutation studies indicating that Nsp9 is a key ingredient that intimately engages other proteins in the replicase complex to mediate efficient virus transcription and replication.

Pssm-ID: 409330 Cd Length: 108 Bit Score: 215.64 E-value: 1.02e-64

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3770 NNEILPGKLKEKAVKASATIdgdAYGSGKALMASESGKSFIYAFVASDSNLKYVKWESNNDLIPIELEAPLRFYVDGVNG 3849
Cdd:cd21897     1 NNEIMPGKLKQRAVKAEGDG---FSGDGKALYNNEGGKTFMYAFIADKPDLKYVKWEFDGGCNTIELEPPCKFLVDTPNG 77

                          90       100       110
                  ....*....|....*....|....*....|.
gi 240015189 3850 PEVKYLYFVKNLNTLRRGAVLGYIGATVRLQ 3880
Cdd:cd21897    78 PQIKYLYFVKNLNTLRRGAVLGYIGATVRLQ 108

CoV_NSP4_C

pfam16348

Coronavirus replicase NSP4, C-terminal; This is the C-terminal domain of the coronavirus ...

2803-2894

1.97e-49

Coronavirus replicase NSP4, C-terminal; This is the C-terminal domain of the coronavirus nonstructural protein 4 (NSP4). NSP4 is encoded by ORF1a/1ab and proteolytically released from the pp1a/1ab polyprotein. It is a membrane-spanning protein which is thought to anchor the viral replication-transcription complex (RTC) to modified endoplasmic reticulum membranes. This predominantly alpha-helical domain may be involved in protein-protein interactions. It has been shown that in Betacoronavirus, the coexpression of NSP3 and NSP4 results in a membrane rearrangement to induce double-membrane vesicles (DMVs) and convoluted membranes (CMs), playing a critical role in SARS-CoV replication. There are two well conserved amino acid residues (H120 and F121) in NSP4 among Betacoronavirus, essential for membrane rearrangements during interaction with NSP3.

Pssm-ID: 465099 Cd Length: 92 Bit Score: 171.17 E-value: 1.97e-49

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  2803 GDKFVGSFESAAMGTFVIDMRSYETLVNSTSLDRIKSYANSFNKYKYYTGSMGEADYRMACYAHLGKALMDYSVSRNDML 2882
Cdd:pfam16348    1 GDKFVGTFEEAALGTFVIDKESYEKLKNSISLDKFNRYLSLYNKYKYYSGKMDEADYREACCAHLAKALEDFSNSGNDVL 80

                           90
                   ....*....|..
gi 240015189  2883 YTPPTVSVNSTL 2894
Cdd:pfam16348   81 YTPPTVSVTSSL 92

Macro_X_Nsp3-like

cd21557

X-domain (or Mac1 domain) of viral non-structural protein 3 and related macrodomains; The ...

1355-1482

6.99e-48

X-domain (or Mac1 domain) of viral non-structural protein 3 and related macrodomains; The X-domain, also called Mac1, is the macrodomain found in riboviral non-structural protein 3 (Nsp3), including the Nsp3 of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) as well as SARS-CoV-2, and other coronaviruses (alpha-, beta-, gamma-, and deltacoronavirus), among others. The SARS-CoV-2 Nsp3 Mac1 is highly conserved among all CoVs, and binds to and hydrolyzes mono-ADP-ribose (MAR) from target proteins. It appears to counter host-mediated antiviral ADP-ribosylation, a post-translational modification that is part of the host response to viral infections. Mac1 is essential for pathogenesis in multiple animal models of CoV infection, implicating it as a virulence factor and potential therapeutic target. Assays show that the de-MARylating activity leads to a rapid loss of substrate, and that Mac1 could not hydrolyze poly-ADP-ribose; thus, Mac1 is a MAR-hydrolase (mono-ADP ribosylhydrolase). Mac1 was originally named ADP-ribose-1"-phosphatase (ADRP) based on data demonstrating that it could remove the phosphate group from ADP-ribose-1"-phosphate; however, activity was modest and was unclear why this would impact a virus infection. This family also includes the X-domain of Avian infectious bronchitis virus (IBV) strain Beaudette coronavirus that does not bind ADP-ribose; the triple glycine sequence found in the X-domains of SARS-CoV and human coronavirus 229E (HCoV229E), which are involved in ADP-ribose binding, is not conserved in the IBV X-domain. SARS-CoVs have two other macrodomains referred to as the SUD-N (N-terminal subdomain, or Mac2) and SUD-M (middle SUD subdomain, or Mac3) of the SARS-unique domain (SUD), which also do not bind ADP-ribose; these bind G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). SARS-CoV SUD-N and SUD-M are not included in this group.

Pssm-ID: 438957 Cd Length: 127 Bit Score: 168.12 E-value: 6.99e-48

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1355 PDVVVNAANGDLRHLGGVAKAIDNFTGGKLTKRSkDYLKSNKSIAPGNAVLFENVLEHLSVLNAVGPRNGDSRVEGKLCN 1434
Cdd:cd21557     1 EDVVVNAANENLKHGGGVAGAIYKATGGAFQKES-DYIKKNGPLKVGTAVLLPGHGLAKNIIHVVGPRKRKGQDDQLLAA 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 240015189 1435 VYKAIAKCDGKILTPLISVGIFNVKLEVSLQCLLKTVTDRDLNVFVYT 1482
Cdd:cd21557    80 AYKAVNKEYGSVLTPLLSAGIFGVPPEQSLNALLDAVDTTDADVTVYC 127

alphaCoV_Nsp7

cd21826

alphacoronavirus non-structural protein 7; This model represents the non-structural protein 7 ...

3492-3574

3.73e-47

alphacoronavirus non-structural protein 7; This model represents the non-structural protein 7 (Nsp7) of alphacoronaviruses that include Feline infectious peritonitis virus (FCoV), Human coronavirus NL63 (HCoV-NL63), and Porcine transmissible gastroenteritis coronavirus (TGEV), among others. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9 and Nsp10 form functional complexes with CoV core enzymes and stimulate replication. Most importantly, a complex of Nsp7 with Nsp8 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the NSP7- or NSP8-coding region have been shown to delay virus growth. Nsp7 and Nsp8 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp7 with Nsp8 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp7 has a 4-helical bundle conformation which is strongly affected by its interaction with Nsp8, especially where it concerns alpha-helix 4. FCoV Nsp7 forms a 2:1 heterotrimer with Nsp8; the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to template length.

Pssm-ID: 409252 Cd Length: 83 Bit Score: 164.46 E-value: 3.73e-47

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3492 SKLTEMKCTNVVLLGLLSKMHVESNSKEWNYCVGLHNEINLCDDPEVVLEKLLALIAFFLSKHNTCDLSDLIDSYFENTT 3571
Cdd:cd21826     1 SKLTDIKCTNVVLLGCLSSMNVAANSKEWAYCVDLHNKINLCDDPEKAQEMLLALLAFFLSKQKDFGLDDLLDSYFDNNS 80


                  ...
gi 240015189 3572 ILQ 3574
Cdd:cd21826    81 ILQ 83

CoV_NSP2_C

Coronavirus replicase NSP2, C-terminal; This entry corresponds to a presumed domain found at ...

731-879

1.29e-23

Coronavirus replicase NSP2, C-terminal; This entry corresponds to a presumed domain found at the C-terminus of Coronavirus non-structural protein 2 (NSP2). NSP2 is encoded by ORF1a/1ab and proteolytically released from the pp1a/1ab polyprotein. The function of NSP2 is uncertain. This presumed domain is found in two copies in some viral NSP2 proteins. This domain is found in both alpha and betacoronaviruses.

Pssm-ID: 465996 Cd Length: 156 Bit Score: 100.03 E-value: 1.29e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189   731 LSNVKIMLGNGVKVF--CDGCNSFAKRLTVSYSKLCDTARKDVEIGGLPFSTfktpASSFIDMKDAIYSVV--------E 800
Cdd:pfam19212    1 LKNAKFTVVNGGIVFvvPKKFKSLVGTLLDLLNKLFDSLVDTVKIAGVKFKA----GGTYYLFSNALVKVVsvklkgkkQ 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189   801 YG-----EAFSFKTANVPVTNSgTIKNDDwsdpILLEPADYVEP-KDNGDVIVIAGYTFYKDEDDHFYPYGSGMVVQKMY 874
Cdd:pfam19212   77 AGlkgakEATVFVGATVPVTPT-RVEVVT----VELEEVDYVPPpVVVGYVVVIDGYAFYKSGDEYYPASTDGVVVPPVF 151


                   ....*
gi 240015189   875 NKMGG 879
Cdd:pfam19212  152 KLKGG 156

CoV_PLPro super family

cl40457

Coronavirus (CoV) papain-like protease (PLPro); This model represents the papain-like protease ...

1096-1279

6.23e-23

Coronavirus (CoV) papain-like protease (PLPro); This model represents the papain-like protease (PLPro) found in non-structural protein 3 (Nsp3) of alpha-, beta-, gamma-, and deltacoronavirus, including highly pathogenic betacoronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. PLPro is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. PLPro, which belongs to the MEROPS peptidase C16 family, participates in the proteolytic processing of the N-terminal region of the replicase polyprotein; it can cleave Nsp1|Nsp2, Nsp2|Nsp3, and Nsp3|Nsp4 sites and its activity is dependent on zinc. Besides cleaving the polyproteins, PLPro also possesses a related enzymatic activity to promote virus replication: deubiquitinating (DUB) and de-ISGylating activities. Both, ubiquitin (Ub) and Ub-like interferon-stimulated gene product 15 (ISG15), are involved in preventing viral infection; coronaviruses utilize Ubl-conjugating pathways to counter the pro-inflammatory properties of Ubl-conjugated host proteins via the action of PLPro, which processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. The Nsp3 PLPro domain in many of these CoVs has also been shown to antagonize host innate immune induction of type I interferon by interacting with IRF3 and blocking its activation.

The actual alignment was detected with superfamily member cd21731:

Pssm-ID: 424088 Cd Length: 289 Bit Score: 101.93 E-value: 6.23e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1096 FKTTDLNGKIILKQQDNNCWVNACCYQLQ------AFEFFNhDLWDDFKKGDVMPFVNFCYAALTLKQGDSGDAEHLLeT 1169
Cdd:cd21731    82 FESDIVNGKRVLKQSDNNCWVNAVCLQLQfakptfKSEGLQ-ALWNKFLTGDVAGFVHWLYWITGANKGDPGDAENTL-N 159

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1170 MLNDY--STAKVTLS--AKCGCGVKEIVLERTVFKLTPLRNEFKYGVCGDCKQINmCKFASVEGSGVFVHdrIEKQTPVS 1245
Cdd:cd21731   160 KLSKYlvSSGSVTVErtTGCDSCNSKRTVTTPVVNASVLRSGVDDGVCKHGVKVT-TRVVSVKGTVIITS--VGKPVVSD 236

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 240015189 1246 QFI-VTPTMHAVYTGTIQNGHYMIEDCIHDYCVDG 1279
Cdd:cd21731   237 ALLlLDGVSYTAFSGDVDNGHYTVYDKATGKVYDG 271

Name

Accession

Description

Interval

E-value

TM_Y_alphaCoV_Nsp3_C

cd21712

C-terminus of alphacoronavirus non-structural protein 3, including transmembrane and Y domains; ...

1899-2399

0e+00

Pssm-ID: 409660 Cd Length: 501 Bit Score: 779.89 E-value: 0e+00

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1899 VRQLNKPALWRYAKLVLLLIALYHFFYLFVSIPLVHKLACSGSVQAYSNSSFVKSEVCGNSILCKACLASYDELADFDHL 1978
Cdd:cd21712     1 VIKLKKKKVWFFAKLLLLLYALYALLFMFVRFPPLNSSLCSGYVDGYANSSFVKSEVCGNSLLCKACLAGYDELSDFPHL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1979 QVSWDYKSDPLWNRVMQLSYFTFLAVFGNNYVRFCLMYFVTQYLNLWLSYFGYVKYSWFLHVINFESISVEFVIIVIVFE 2058
Cdd:cd21712    81 QVVWDHVSDPLFSNVLPLFYFAFLLIFGNNYVRCFLLYFVAQYINNWGVYFGYQDYSWFLHFVPFDSFSDEIVVIFIVVK 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2059 AVLALKHIFFPCNNPSCKTCSKIARQTRIPIQVVVNGSMKTVYVHANGTGKLCKKHNFYCKNCDSYGFDHTFICDEIVRD 2138
Cdd:cd21712   161 VLLFLKHVIFGCDKPSCKACSKSARLTRIPVQTIVNGSMKSFYVHANGGGKFCKKHNFFCVNCDSYGVGNTFINDEVARE 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2139 LSNSVKQTVYATDKSYQEVTKVECSDGFYRFYVGEEFTAYDYDVKHKKYSSQEVLKTMFLLDDFIVYSPSGSSLASVRNV 2218
Cdd:cd21712   241 LSNVVKTTVQPTGPAYIEVDKVEFSNGFYYLYSGDTFWRYNFDITEKKYSCKEVLKNCNLLDDFIVYNNNGSNVAQVKNA 320

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2219 CVYFSQLIGRPIKIVNSDLLEDLSVDFKGALFNAKKNVIKNSFNVDVSECKNLEECYKACNLDVTFSTFEMAINNAHRFG 2298
Cdd:cd21712   321 CVYFSQLLCKPIKLVDSALLSSLSVDFNGALHKAFVKVLKNSFNKDLSNCKTLEECKKALGLDVSDDEFESAVSNAHRYD 400

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2299 ILITDRSFNNFWPSKIKPGSSgVSAMDIGKCMTFDAKIVNAKVLTQRGKSVVWLSQDFSALSSTAQKVLVKTFVEEGVNF 2378
Cdd:cd21712   401 VLLTDRSFNNFVTSYAKPEEK-LSTHDIAVCMRAGAKVVNHNVLTKENVPIVWLAKDFSALSEEARKYIVKTTKAKGVNF 479

                         490       500
                  ....*....|....*....|.
gi 240015189 2379 SLTFNAVGSDEDLPYERFTES 2399
Cdd:cd21712   480 LLTFNDNRMTTTLPAVSIVSK 500

alphaCoV_Nsp2_HCoV-229E-like

cd21514

alphacoronavirus non-structural protein 2 (Nsp2), similar to HCoV-229E Nsp2 and related ...

110-715

0e+00

Pssm-ID: 394865 Cd Length: 503 Bit Score: 617.35 E-value: 0e+00

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  110 GAIYVDQYMCGADGKPVIEG---EFKDYFGDEDVIIYEGEEYHCAWLTVRDDKPLCQQTLLTIREIQYNLDIPHKLPNCA 186
Cdd:cd21514     1 NTVYVDQYMCGADGKPVLPEdewEFKDYFGDLDEIVINGITYVKAWDVERKDVPYEKQNLLSIESITYLSDIPHTLADGA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  187 IREVAPPVKKNSKVVLSEEYRKLYDIFGSPFMSNGDSLNKCFDSLHFIAATLKCPCGSESSGVGDWTGFKTACCGLHGKV 266
Cdd:cd21514    81 VLRVAKPPKKSKKVVLSEPYKKLYDAFGSPFVTNGSTLLEVVTKPVFIHALVKCKCGKESWTVGDWTGYKSSCCGVPCKP 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  267 KGVTLGAVKPGDAVVTSMSAGKGVKFFANSVLQYAGDVENVSVWKVIKTFTVNETVCTTDFEGELNdfikpESTSPVSCS 346
Cdd:cd21514   161 ICVVVGSVKPGDVVVTSLGAGSGVKYYNGMVLKHVCDVDGVSIWRVIKVQSVDGFVASGNFDEELH-----SELSLDACS 235

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  347 IKRafitgevddavhdciitgkldlstnlfgsanllfkKTPWFVQKCGAIFADAWKVVEELLCSLKLTYKQIYDVVASLC 426
Cdd:cd21514   236 FTN-----------------------------------DKPWFVRKLGDLFESAWDAFVAAVKSLKVTSKQLVDLVKALC 280

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  427 TSAFTIMDYKPVFVVSHSS-VKNLVDKCVKILVKAFDVFTQTITIAGveaKCFVLGSKYLLFNNALVKLVSVKILGKRQK 505
Cdd:cd21514   281 SAALTVVNGVIVFVADVPEkFKSAFEKFVSFVVGLFDLTCDTVKVAG---KKFKRVGDYVLLNNALVKLVSVKVKGVRQA 357

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  506 GLDSAFFVTNLIGATVNVTPQRTEAANISLNKVD-DVVTPGEGHIVIVGGMAFYKSEEYYFMMASPDSVLVNNVFKAarv 584
Cdd:cd21514   358 GLKTAQYATVVVGKTTKVTSSRVEVATVNLVLVDeDVPLPGEGYTVVIGGQAFFCSGGYYRLMADPDEVLETPVFKA--- 434

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  585 psynivydvddntkskmvvkigtsfdfdgdldaaiakvndlliefrqeklcfralkdgenilveayfkkYKMPVCLKNHV 664
Cdd:cd21514   435 ---------------------------------------------------------------------FKAPSYIKDEV 445

                         570       580       590       600       610
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 240015189  665 GLWDIVRRDSDKKGFLDTFNHLNDLEDVKETK-------IQAIKNILCPDLLLELDFG 715
Cdd:cd21514   446 EFVDLCEKYVGEPGFDEFYVAAHEALDLDQFEvalfsfdKVDEKEPECPELLLEIDGG 503

CoV_NSP3_C

pfam19218

Coronavirus replicase NSP3, C-terminal; This family represents the C-terminal region of ...

1935-2383

0e+00

Coronavirus replicase NSP3, C-terminal; This family represents the C-terminal region of non-structural protein NSP3 (also known as nsp3). NSP3 is the product of ORF1a. It is found in human SARS coronavirus polyprotein 1a and 1ab, and in related coronavirus polyproteins. It is a multifunctional protein comprising up to 16 different domains and regions. NSP3 binds to viral RNA, nucleocapsid protein, as well as other viral proteins and participates in polyprotein processing.

Pssm-ID: 466002 Cd Length: 463 Bit Score: 616.27 E-value: 0e+00

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  1935 KLACSGSVQAYSNSSFVKSEVCGNSILCKACLASYDELADFDHLQVSWDYKSDPLWNRVMQLSYFTF-----LAVFGNNY 2009
Cdd:pfam19218    1 GYPCDGYVDGYSNSSFNKSDYCNGSILCKACLSGYDSLHDYPHLKVVQQPVKDPLFVDVTPLFYFAIelfvaLALFGGTF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  2010 VRFCLMYFVTQYLNLWLSYFGYVKYSWFLHVINFESISVEFVIIVIVFEAVLALKHIFFPCNNPSCKTCSKIARQTRIPI 2089
Cdd:pfam19218   81 VRVFLLYFLQQYVNFFGVYLGLQDYSWFLTLIPFDSFLREYVVLFYVIKLYRFLKHVVFGCKKPSCLACSKSARLTRVPV 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  2090 QVVVNGSMKTVYVHANGTGKLCKKHNFYCKNCDSYGFDHTFICDEIVRDLSNSVKQTVYATDKSYQEVTKVECSDGFYRF 2169
Cdd:pfam19218  161 STVVNGSKKSFYVNANGGTKFCKKHNFFCKNCDSYGPGNTFINDEVAEDLSNVTKRSVKPTDPAYYEVDKVEFQNGFYYL 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  2170 YVGEEFTAYDYDVKHKKYSSQEVLKTMFL----LDDFIVYSPSGSSLASVRNVCVYFSQLIGRPIKIVNSDLLEDL--SV 2243
Cdd:pfam19218  241 YSGREFWRYYFDVTVSKYSDKEVLKNCNIkgypLDDFIVYNSNGSNLAQAKNACVYYSQLLCKPIKLVDSNLLSSLgdSV 320

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  2244 DFKGALFNAKKNVIKNSFNVDVSECKNLEECYKACNLDVTFSTFEMAINNAHRFGILITDRSFNNFWPSKIKPGSSgVSA 2323
Cdd:pfam19218  321 DVNGALHDAFVEVLLNSFNVDLSKCKTLIECKKDLGSDVDTDSFVNAVLNAHRYDVLLTDDSFNNFVPTYAKPEDS-LST 399

                          410       420       430       440       450       460
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  2324 MDIGKCMTFDAKIVNAKVLTQRGKSVVWLSQDFSALSSTAQKVLVKTFVEEGVNFSLTFN 2383
Cdd:pfam19218  400 HDLAVCIRFGAKIVNHNVLKKENVPVVWSADDFLKLSEEARKYIVKTAKKKGVTFMLTFN 459

alphaCoV_Nsp5_Mpro

cd21665

alphacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily ...

2898-3193

0e+00

Pssm-ID: 394886 Cd Length: 296 Bit Score: 589.26 E-value: 0e+00

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2898 LRKMAQPSGIVEPCIVRVAYGNNVLNGLWIGDEVICPRHVIASDTSRVINYENELSSVRLHNFSIAKNNVFLGVVSVKYK 2977
Cdd:cd21665     1 LRKMAQPSGVVEKCVVRVSYGNMVLNGLWLGDTVYCPRHVIASDTTSTIDYDHEYSLMRLHNFSISVGNVFLGVVGVTMR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2978 GVNLVLKVNQVNPNTPEHKFKSVKPGESFNILACYEGCPGSVYGVNMRSQGTIKGSFIAGTCGSVGYVLENGTLYFVYMH 3057
Cdd:cd21665    81 GALLVIKVNQNNVNTPKYTFRTLKPGDSFNILACYDGVPSGVYGVNMRTNYTIKGSFINGACGSPGYNLNNGTVEFCYMH 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3058 HLELGNGSHVGSNLEGEMYGGYEDQPSMQLEGTNVMSSDNVVAFLYAALINGERWFVTNASMSLESYNAWAKTNSFTEIV 3137
Cdd:cd21665   161 QLELGSGCHVGSDLDGVMYGGYEDQPTLQVEGANVLVTENVVAFLYAALLNGCNWWLSSDRVTVEAFNEWAVANGFTTVS 240

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 240015189 3138 STDAFNMLAAKTGYSVEKLLECIVRLNKGFGGRTILSYGSLCDEFTPTEVIRQMYG 3193
Cdd:cd21665   241 STDCFSILAAKTGVDVERLLAAIQRLSKGFGGKTILGYTSLTDEFTLSEVIKQMYG 296

Peptidase_C30

pfam05409

Coronavirus endopeptidase C30; This Coronavirus (CoV) domain, peptidase C30, is also known as ...

2924-3197

7.73e-168

Coronavirus endopeptidase C30; This Coronavirus (CoV) domain, peptidase C30, is also known as 3C-like proteinase (3CL-pro), or CoV main protease (M-pro) domain. CoV M-pro is a dimer where each subunit is composed of three domains I, II and III,,. Domains I and II consist of six-stranded antiparallel beta barrels and together resemble the architecture of chymotrypsin, and of picornaviruses 3C proteinases. The substrate-binding site is located in a cleft between these two domains. The catalytic site is situated at the centre of the cleft. A long loop connects domain II to the C-terminal domain (domain III). This latter domain has been implicated in the proteolytic activity of M-pro. In the active site of M-pro, Cys and His form a catalytic dyad,.

Pssm-ID: 398852 Cd Length: 274 Bit Score: 518.15 E-value: 7.73e-168

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  2924 GLWIGDEVICPRHVIASDTSRVINYENELSSVRLHNFSIAKNNVFLGVVSVKYKGVNLVLKVNQVNPNTPEHKFKSVKPG 3003
Cdd:pfam05409    1 GLWLGDTVYCPRHVIGSFTGMLPQYEHLLSIARNHDFCVVSGGVQLTVVSAKMQGAILVLKVHTNNPNTPKYKFVRLKPG 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  3004 ESFNILACYEGCPGSVYGVNMRSQGTIKGSFIAGTCGSVGYVLENGTLYFVYMHHLELGNGSHVGSNLEGEMYGGYEDQP 3083
Cdd:pfam05409   81 ESFTILAAYDGCPQGVYHVTMRSNHTIKGSFLNGACGSVGYNLKGGTVCFVYMHHLELPNGSHTGTDLEGVFYGPYVDEE 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  3084 SMQLEGTNVMSSDNVVAFLYAALINGERWFVTNASMSLESYNAWAKTNSFTEIVSTDAFNMLAAKTGYSVEKLLECIVRL 3163
Cdd:pfam05409  161 VAQLEGTDQTYTDNVVAWLYAAIINGPRWFLASTTVSLEDFNAWAMTNGFTPFPCEDAILGLAAKTGVSVERLLAAIKVL 240

                          250       260       270
                   ....*....|....*....|....*....|....
gi 240015189  3164 NKGFGGRTILSYGSLCDEFTPTEVIRQMYGVNLQ 3197
Cdd:pfam05409  241 NNGFGGRTILGSPSLEDEFTPEDVYNQMAGVTLQ 274

cv_Nsp4_TM

cd21473

coronavirus non-structural protein 4 (Nsp4) transmembrane domain; Nsp4 may be involved in ...

2419-2792

1.48e-161

Pssm-ID: 394836 Cd Length: 376 Bit Score: 504.82 E-value: 1.48e-161

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2419 FWCLVFFIIIYGLCSVYSVATQSYIdSAEGYDYMVIKNGVVQPFDDSINCVHNTYKGFAVWFKAKYGFIPTFDKSCPIVL 2498
Cdd:cd21473     2 LWLLLAAILLYAFLPSYSVFTVTVS-SFPGYDFKVIENGVLRDIRSTDTCFANKFVNFDSWYQAKYGSVPTNSKSCPIVV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2499 GTVFDLGNMrpIPDVPAYVALVGRSLVFAINAA-FGVTNVCYDHTGAAVSKNSYFDTCVFNSACTTLAGLGGTVVYCAKQ 2577
Cdd:cd21473    81 GVIDDVRGS--VPGVPAGVLLVGKTLVHFVQTVfFGDTVVCYTPDGVITYDSFYTSACVFNSACTYLTGLGGRQLYCYDT 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2578 GLVEGAKLYSELMPDYYYEHASGNMVKIPAIVRGFGLRFVKTQATTYCRVGECIESQAGFCFGGDNWFVYDKEF-GDGYI 2656
Cdd:cd21473   159 GLVEGAKLYSDLLPHVRYKLVDGNYIKFPEVILEGGPRIVRTLATTYCRVGECEDSKAGVCVSFDGFWVYNNDYyGPGVY 238

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2657 CGSSALGFFKNVFALFNSNMSVVATSGAMLANIIIACLAIAVCYGVLKFKKIFGDCTLLVVMIIVTLVVNNVSYFVTQNT 2736
Cdd:cd21473   239 CGDGLFDLLTNLLSGFFQPVSVFALSGQLLFNTIVAILAVLACYYVQKFKRAFGDMSVVVVTVVAAALVNNVLYVVTQNP 318

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 240015189 2737 LFMIVYAIIYYFTTRKFAY--PGILDAGFIIAYMNMAPWYVLVLYIMVFLYDSLPSLF 2792
Cdd:cd21473   319 LLMIVYAVLYFYATLYLTYerAWIMHLGWVVAYGPIAPWWLLALYVVAVLYDYLPWFF 376

CoV_NSP4_N

pfam19217

Coronavirus replicase NSP4, N-terminal; This is the N-terminal domain of the coronavirus ...

2430-2777

1.07e-144

Coronavirus replicase NSP4, N-terminal; This is the N-terminal domain of the coronavirus nonstructural protein 4 (NSP4). NSP4 is encoded by ORF1a/1ab and proteolytically released from the pp1a/1ab polyprotein. NSP4 is a membrane-spanning protein which is thought to anchor the viral replication-transcription complex to modified endoplasmic reticulum membranes. This N-terminal region represents the membrane spanning region, covering four transmembrane regions.

Pssm-ID: 466001 Cd Length: 351 Bit Score: 455.19 E-value: 1.07e-144

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  2430 GLCSVYSVATQSYIDSAEGYDYMVIKNGVVQPFDDSINCVHNTYKGFAVWFKAKYGFiPTFDKSCPIVLGTVF-DLGNMr 2508
Cdd:pfam19217    1 YALSPTFFNTVVYFVSDPVYDFKVIENGVLRDFRSTDTCFHNKFDNFDSWHQAKFGS-PTNSRSCPIVVGVVDeVVGRV- 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  2509 pIPDVPAYVALV-GRSLVFAINAAFGVTNVCYDHTGAAVSKNSYFDTCVFNSACTTLAGLGGT-VVYCAKQGLVEGAKLY 2586
Cdd:pfam19217   79 -VPGVPAGVALVgGTILHFVTRVFFGAGNVCYTPSGVVTYESFSASACVFNSACTTLTGLGGTrVLYCYDDGLVEGAKLY 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  2587 SELMPDYYYEHASGNMVKIPAIVRGFGLRFVKTQATTYCRVGECIESQAGFCFGGDNWFVYDKEFGDGYICGSSALGFFK 2666
Cdd:pfam19217  158 SDLVPHVRYKLVDGNYVKLPEVLFRGGFRIVRTLATTYCRVGECEDSKAGVCVGFDRSFVYNNDFGPGVYCGSGFLSLLT 237

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  2667 NVFALFNSNMSVVATSGAMLANIIIACLAIAVCYGVLKFKKIFGDCTLLVVMIIVTLVVNNVSYFVTQ-NTLFMIVYAII 2745
Cdd:pfam19217  238 NVFSGFNTPISVFALTGQLMFNCVVALIAVCVCYYVLKFKRAFGDYSTGVLTVVLATLVNNLSYFVTQvNPVLMIVYAVL 317

                          330       340       350
                   ....*....|....*....|....*....|....
gi 240015189  2746 YYFTTRKFAYP--GILDAGFIIAYMNMAPWYVLV 2777
Cdd:pfam19217  318 YFYATLYVTPEyaWIWHLGFLVAYVPLAPWWVLL 351

alphaCoV-Nsp6

cd21558

alphacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host ...

3182-3491

2.82e-136

Pssm-ID: 394844 Cd Length: 293 Bit Score: 428.54 E-value: 2.82e-136

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3182 FTPTEVIRQMYGVNLQSGKVKSLFYPVMTAIAILFAFWLEFFMYTPFTWINPAFVSVILAITTLVSAVLVVGIKHKMLFF 3261
Cdd:cd21558     1 FTTSEVIKQMYGVNLQSGKVKSAFKNVLLVGVFLFMFWSELLMYTSFFWINPGLVTPVFLVLVLVSLLLTLFLKHKMLFL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3262 MSFVMPSVILATAHNVVWDMtYYESLQALVENVNTTFLPVDMQGVMLALFCVVVFVTYTIRFFTCKQSWFSLFVTTVFVM 3341
Cdd:cd21558    81 QTFLLPSVIVTAFYNLAWDY-YVTAVLAEYFDYHVSLMSFDIQGVLNIFVCLFVFFLHTYRFVTSGTSWFTYVVSLVFVL 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3342 FNIVKLLGmigepwtddhillcLVNMLTMLISLTTKDWFVVFVSYKVAYYIVVyvMHPAFVQDFGFIKCVSIIYMACGYL 3421
Cdd:cd21558   160 YNYFYGND--------------YLSLLMMVLSSITNNWYVGAIAYKLAYYIVY--VPPSLVADFGTVKAVMLVYVALGYL 223

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3422 FCCYYGILYWVNRFTCMTCGVYQFTVSPAELKYMTANNLSAPKTAYDAMILSVKLMGIGGERNIKISTVQ 3491
Cdd:cd21558   224 CCVYYGILYWINRFTKLTLGVYDFKVSAAEFKYMVANGLKAPTGVFDALLLSFKLIGIGGERTIKISTVQ 293

alphaCoV_PLPro

alphacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...

1495-1781

9.60e-134

Pssm-ID: 409648 Cd Length: 289 Bit Score: 421.26 E-value: 9.60e-134

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1495 GTIPVKVTEDTVNQKRVSVALDKTYGEQLkGTVVIKDKDVTNQ-LPSVSDAGEKVvkALDVDWNAYYGFPNAAAFSASSH 1573
Cdd:cd21731     1 KSVVVKVTEDGRNVKDVVVDTDKTFGEQL-GVCSVNDKDVTGVvPPDDSDKVVSV--APDVDWDSHYGFPNAAVFHTLDH 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1574 DAYKFDVVTHNNFIVHKQTDNNCWVNAICLALQRLKPTWKFPGVKSLWDVFLTRKTAGFVHMLYHISGLKKGQPGDAELT 1653
Cdd:cd21731    78 SAYAFESDIVNGKRVLKQSDNNCWVNAVCLQLQFAKPTFKSEGLQALWNKFLTGDVAGFVHWLYWITGANKGDPGDAENT 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1654 LHKLGELMVSDSIVTITHTTACDKCAKIENFTGPVV-AAPLMIYGTDETCVHGVSVNVKVTSIRGTVAITSLIGPVVGDV 1732
Cdd:cd21731   158 LNKLSKYLVSSGSVTVERTTGCDSCNSKRTVTTPVVnASVLRSGVDDGVCKHGVKVTTRVVSVKGTVIITSVGKPVVSDA 237

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 240015189 1733 ---IDATGYICYTGLNSRGHYTYYDNRNGLMVDAEKAYHFEKNLLQVTTAIA 1781
Cdd:cd21731   238 lllLDGVSYTAFSGDVDNGHYTVYDKATGKVYDGDKTVSFKLDLLSVTSVVV 289

alphaCoV_Nsp8

cd21830

alphacoronavirus non-structural protein 8; This model represents the non-structural protein 8 ...

3575-3769

2.24e-126

Pssm-ID: 409257 Cd Length: 195 Bit Score: 395.95 E-value: 2.24e-126

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3575 SVASAYAALPSWIAYEKARADLEEAKKNDVSPQLLKQLTKACNIAKSEFEREVSVQKKLDKMAEQAAASMYKEARAVDRK 3654
Cdd:cd21830     1 SVASTFANMPSFIAYETARQDYEDAVKNGSSPQLIKQLKKAMNIAKSEFDREASVQRKLDRMAEQAAAQMYKEARAVNRK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3655 SKIVSAMHSLLFGMLKKLDMSSVNTIIEQARNGVLPLSIIPAASATRLIVVTPNLEVLSKVRQENNVHYAGAIWSIVEVK 3734
Cdd:cd21830    81 SKVISAMHSLLFGMLRRLDMSSVDTILNLAKDGVVPLSIIPAASATRLVVVVPDLESFSKIRRDGCVHYAGVVWTIVDIK 160

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 240015189 3735 DANGSQVHLKEVTAANELNITWPLSITCERTTKLQ 3769
Cdd:cd21830   161 DNDGKVVHLKEVTAANEESLAWPLHLNCERIVKLQ 195

CoV_NSP8

pfam08717

Coronavirus replicase NSP8; Viral NSP8 (non structural protein 8) forms a hexadecameric ...

3575-3765

1.17e-109

Coronavirus replicase NSP8; Viral NSP8 (non structural protein 8) forms a hexadecameric supercomplex with NSP7 that adopts a hollow cylinder-like structure. The dimensions of the central channel and positive electrostatic properties of the cylinder imply that it confers processivity on RNA-dependent RNA polymerase. NSP7 and NSP8 heterodimers play a role in the stabilization of NSP12 regions involved in RNA binding and are essential for a highly active NSP12 polymerase complex. It has been demonstrated that NSP8 acts as an oligo(U)-templated polyadenylyltransferase but also has robust (mono/oligo) adenylate transferase activities. NSP8 has N- and C-terminal D/ExD/E conserved motifs, being the N-terminal motif critical for RNA polymerase activity as these residues are part of the Mg2-binding active site.

Pssm-ID: 400866 Cd Length: 197 Bit Score: 347.99 E-value: 1.17e-109

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  3575 SVASAYAALPSWIAYEKARADLEEAKKNDVSPQLLKQLTKACNIAKSEFEREVSVQKKLDKMAEQAAASMYKEARAVDRK 3654
Cdd:pfam08717    1 SVASEFSSLPSYAAYETAKEAYEEAVANGSSQQVLKQLKKACNIAKSEFDRDAAVQKKLEKMAEQAMTQMYKEARAVDRK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  3655 SKIVSAMHSLLFGMLKKLDMSSVNTIIEQARNGVLPLSIIPAASATRLIVVTPNLEVLSKVRQENNVHYAGAIWSIVEVK 3734
Cdd:pfam08717   81 SKVVSAMHTLLFSMLRKLDNSALNTIINNARNGVVPLNIIPATTAAKLTVVVPDYETFVKVVDGNTVTYAGAVWEIQEVK 160

                          170       180       190
                   ....*....|....*....|....*....|.
gi 240015189  3735 DANGSQVHLKEVTAANELNITWPLSITCERT 3765
Cdd:pfam08717  161 DADGKIVHLKEITMDNSPNLAWPLIVTAERA 191

CoV_NSP6

pfam19213

Coronavirus replicase NSP6; This entry represents proteins found in Coronaviruses and includes ...

3222-3491

6.61e-99

Coronavirus replicase NSP6; This entry represents proteins found in Coronaviruses and includes the Non-structural Protein 6 (NSP6). Coronaviruses encode large replicase polyproteins which are proteolytically processed by viral proteases to generate mature Nonstructural Proteins (NSPs). NSP6 is a membrane protein containing 6 transmembrane domains with a large C-terminal tail. NSP6 from the avian coronavirus, infectious bronchitis virus (IBV) and the mouse hepatitis virus (MHV) have been shown to localize to the ER and to generate autophagosomes. Coronavirus NSP6 proteins have also been shown to limit autophagosome expansion. This may favour coronavirus infection by reducing the ability of autophagosomes to deliver viral components to lysosomes for degradation. NSP6 from IBV, MHV and severe acute respiratory syndrome coronavirus (SARS-CoV) have also been found to activate autophagy.

Pssm-ID: 465997 Cd Length: 260 Bit Score: 319.97 E-value: 6.61e-99

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  3222 FFMYTPFTWINPAFVSVILAITTLVSAVLVVGIKHKMLFFMSFVMPSVILATAHNVVWDMtYYESLQALVENVNTTFLPV 3301
Cdd:pfam19213    1 LLMYTALYWLPPNLITPVLPVLTCVSAILTLFIKHKVLFLTTFLLPSVVVMAYYNFTWDY-YPNSFLRTVYDYHFSLTSF 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  3302 DMQGVMLALFCVVVFVTYTIRFFTCKQSWFSLFVTTVFVMFNIVKLLGMIGEPWTddhillclVNMLTMLISLTTKDWFV 3381
Cdd:pfam19213   80 DLQGYFNIASCVFVNVLHTYRFVRSKYSIATYLVSLVVSVYMYVIGYALLTATDV--------LSLLFMVLSLLTSYWYV 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  3382 VFVSYKVAYYIVVYvMHPAFVQDFGFIKCVSIIYMACGYLFCCYYGILYWVNRFTCMTCGVYQFTVSPAELKYMTANNLS 3461
Cdd:pfam19213  152 GAIAYKLAKYIVVY-VPPSLIAVFGDIKVVLLVYVCIGYVCCVYFGILYWINRFTKLTLGVYDFKVSAAEFKYMVANGLS 230

                          250       260       270
                   ....*....|....*....|....*....|
gi 240015189  3462 APKTAYDAMILSVKLMGIGGERNIKISTVQ 3491
Cdd:pfam19213  231 APRNVFEALILNFKLLGIGGNRTIKISTVQ 260

CoV_NSP2_N

pfam19211

Coronavirus replicase NSP2, N-terminal; This entry corresponds to the N-terminal region of ...

111-310

4.01e-95

Coronavirus replicase NSP2, N-terminal; This entry corresponds to the N-terminal region of coronavirus non-structural protein 2. NSP2 is encoded by ORF1a/1ab and proteolytically released from the pp1a/1ab polyprotein. The function of this protein is uncertain. This region contains numerous conserved and semi-conserved cysteine residues.

Pssm-ID: 465995 [Multi-domain] Cd Length: 204 Bit Score: 306.58 E-value: 4.01e-95

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189   111 AIYVDQYMCGADGKPVIEG---EFKDYFGDEDVIIYEGEEYHCAWLTVRDDKPLCQQTLLTIREIQYNLDIPHKLPNCAI 187
Cdd:pfam19211    2 VIPVDQYMCGADGKPVLPEdtwCFKDYFGDDGEIVLNGGTYRKAWKVVRKNVPYPKQSLFTINSITYLGDIPHVLPNGAV 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189   188 REVAPPVKKNSKVVLSEEYRKLYDIFGSPFMSNGDSLNKCFDSLHFIAATLKCPCGSESSGVGDWTGFKTACCGLHGKVK 267
Cdd:pfam19211   82 LHVAPRVKKSKKVVLSEKYKSLYDTYGSPFVTNGSTLLEIVPKPVFHHALVKCSCGRESWTVGDWSGFKCLCCGVYGKPI 161

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|...
gi 240015189   268 GVTLGAVKPGDAVVTSMSAGKGVKFFANSVLQYAGDVENVSVW 310
Cdd:pfam19211  162 CVSAGDVKPGDVLITKAPVGRGKKFFGGAVLKYVGCVEGVSVW 204

alpha_betaCoV_Nsp10

cd21901

alphacoronavirus and betacoronavirus non-structural protein 10; This model represents the ...

3881-4010

5.81e-93

Pssm-ID: 409326 Cd Length: 130 Bit Score: 297.27 E-value: 5.81e-93

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3881 AGKPTEHPSNSGLLTLCAFAPDPAKAYVDAVKRGMQPVTNCVKMLSNGAGNGMAVTNGVESNTQQDSYGGASVCIYCRCH 3960
Cdd:cd21901     1 AGKQTEVASNSSLLTLCAFAVDPAKTYLDAVKSGGKPVGNCVKMLTNGTGTGQAITVKPEANTNQDSYGGASVCLYCRAH 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 240015189 3961 VEHPAIDGLCRFKGKFVQVPTGTQDPIRFCIENEICVVCGCWLNNGCMCD 4010
Cdd:cd21901    81 VEHPDMDGVCKLKGKYVQVPLGTNDPVRFCLENDVCKVCGCWLGNGCSCD 130

CoV_NSP10

pfam09401

Coronavirus RNA synthesis protein NSP10; Non-structural protein 10 (NSP10) is involved in RNA ...

3892-4010

6.61e-75

Coronavirus RNA synthesis protein NSP10; Non-structural protein 10 (NSP10) is involved in RNA synthesis. It is synthesized as a polyprotein whose cleavage generates many non-structural proteins. NSP10 contains two zinc binding motifs and forms two anti-parallel helices which are stacked against an irregular beta sheet. A cluster of basic residues on the protein surface suggests a nucleic acid-binding function. NSP10 interacts with NSP14 and NSP16 and regulates their respective ExoN and 2-O-MTase activities. When binding to the N-terminal of NSP14, nsp10 allows the ExoN active site to adopt a stably closed conformation and is an allosteric regulator that stabilizes NSP16. The residue Tyr-96 plays a crucial role in the NSP10-NSP16/NSP14 interaction. This residue is specific for SARS-CoV NSP10 and is a phenylalanine in most other Coronavirus homologs.

Pssm-ID: 462788 Cd Length: 119 Bit Score: 245.04 E-value: 6.61e-75

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  3892 GLLTLCAFAPDPAKAYVDAVKRGMQPVTNCVKMLSNGAGNGMAVTNGVESNTQQDSYGGASVCIYCRCHVEHPAIDGLCR 3971
Cdd:pfam09401    1 SLLSLCAFAVDPAKAYLDYLAQGGQPITNCVKMLCNHAGTGMAITVKPEANTDQDSYGGASVCLYCRAHIEHPNVDGLCQ 80

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 240015189  3972 FKGKFVQVPTGTQDPIRFCIENEICVVCGCWLNNGCMCD 4010
Cdd:pfam09401   81 LKGKFVQIPTGTKDPVSFCLTNTVCTVCGCWLGYGCSCD 119

TGEV-like_alphaCoV_Nsp1

cd21687

non-structural protein 1 from transmissible gastroenteritis virus and similar ...

2-105

2.72e-69

Pssm-ID: 439284 Cd Length: 104 Bit Score: 228.52 E-value: 2.72e-69

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189    2 SSKHFKILVNEDYQVNVPSLPFRDVSQEIKYCYRNGFDGYVFVPEYRRDLVDCNRKDHYVIGVLGNGISDLKPVLLTEPS 81
Cdd:cd21687     1 SSKQFKILVNEDYQVNVPSLPFRDVLQEIKYCYRNGFDGYVFVPEYRRDLVDCDRKDHYVIGVLGNGISDLKPVLLTEPS 80

                          90       100
                  ....*....|....*....|....
gi 240015189   82 VMLQGFIVRANCNGVLEDFDLKIA 105
Cdd:cd21687    81 VMLQGFIVRANCNGVLEDFDLKIA 104

CNV-Replicase_N

pfam16688

Replicase polyprotein N-term from Coronavirus nsp1; CNV-Replicase_N is the N-terminal domain ...

1-108

7.02e-68

Replicase polyprotein N-term from Coronavirus nsp1; CNV-Replicase_N is the N-terminal domain of a family of ssRNA positive-stranded porcine transmissible gastroenteritis coronaviruses. the domain folds into a six-stranded beta-barrel fold with a long alpha helix on the rim of the barrel. This fold is shared with SARS-CoV nsp1.

Pssm-ID: 465234 Cd Length: 108 Bit Score: 224.87 E-value: 7.02e-68

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189     1 MSSKHFKILVNEDYQVNVPSLPFRDVSQEIKYCYRNGFDGYVFVPEYRRDLVDCNRKDHYVIGVLGNGISDLKPVLLTEP 80
Cdd:pfam16688    1 MSSKQFKILVNEDYQVNVPSLPFRDVLQDIKYCYRNGFDGYVFVPEYRRDLVDCNRKDHYVIGVLGNGISDLKPVLLTEP 80

                           90       100
                   ....*....|....*....|....*...
gi 240015189    81 SVMLQGFIVRANCNGVLEDFDLKIARTG 108
Cdd:pfam16688   81 SVMLQGFIVRADCNGVLEDFDLKIARTG 108

alphaCoV_Nsp9

cd21897

alphacoronavirus non-structural protein 9; This model represents the non-structural protein 9 ...

3770-3880

1.02e-64

Pssm-ID: 409330 Cd Length: 108 Bit Score: 215.64 E-value: 1.02e-64

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3770 NNEILPGKLKEKAVKASATIdgdAYGSGKALMASESGKSFIYAFVASDSNLKYVKWESNNDLIPIELEAPLRFYVDGVNG 3849
Cdd:cd21897     1 NNEIMPGKLKQRAVKAEGDG---FSGDGKALYNNEGGKTFMYAFIADKPDLKYVKWEFDGGCNTIELEPPCKFLVDTPNG 77

                          90       100       110
                  ....*....|....*....|....*....|.
gi 240015189 3850 PEVKYLYFVKNLNTLRRGAVLGYIGATVRLQ 3880
Cdd:cd21897    78 PQIKYLYFVKNLNTLRRGAVLGYIGATVRLQ 108

CoV_NSP9

pfam08710

Coronavirus replicase NSP9; Nsp9 is a single-stranded RNA-binding viral protein involved in ...

3770-3880

2.60e-52

Coronavirus replicase NSP9; Nsp9 is a single-stranded RNA-binding viral protein involved in RNA synthesis. Several crystallographic structures of nsp9 have shown that it is composed of seven beta strands and a single alpha helix. Nsp9 proteins have N-finger motifs and highly conserved GXXXG motifs that both play critical roles in dimerization. The conserved helix-helix dimer interface containing a GXXXG protein-protein interaction motif is biologically relevant to SARS-CoV replication.

Pssm-ID: 285872 Cd Length: 111 Bit Score: 180.37 E-value: 2.60e-52

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  3770 NNEILPGKLKEKAVKASATiDGDAYGSGKALMASESGKSFIYAFVASDSNLKYVKWESNND-LIPIELEAPLRFYVDGVN 3848
Cdd:pfam08710    1 NNELMPGKLKTKACKAGVT-DAHCSVEGKAYYNNEGGGSFVYAILSSNPNLKYAKFEKEDGnVIYVELEPPCRFVVDTPK 79

                           90       100       110
                   ....*....|....*....|....*....|..
gi 240015189  3849 GPEVKYLYFVKNLNTLRRGAVLGYIGATVRLQ 3880
Cdd:pfam08710   80 GPEVKYLYFVKNLNNLRRGMVLGYISATVRLQ 111

CoV_NSP4_C

pfam16348

Coronavirus replicase NSP4, C-terminal; This is the C-terminal domain of the coronavirus ...

2803-2894

1.97e-49

Pssm-ID: 465099 Cd Length: 92 Bit Score: 171.17 E-value: 1.97e-49

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  2803 GDKFVGSFESAAMGTFVIDMRSYETLVNSTSLDRIKSYANSFNKYKYYTGSMGEADYRMACYAHLGKALMDYSVSRNDML 2882
Cdd:pfam16348    1 GDKFVGTFEEAALGTFVIDKESYEKLKNSISLDKFNRYLSLYNKYKYYSGKMDEADYREACCAHLAKALEDFSNSGNDVL 80

                           90
                   ....*....|..
gi 240015189  2883 YTPPTVSVNSTL 2894
Cdd:pfam16348   81 YTPPTVSVTSSL 92

Macro_X_Nsp3-like

cd21557

X-domain (or Mac1 domain) of viral non-structural protein 3 and related macrodomains; The ...

1355-1482

6.99e-48

Pssm-ID: 438957 Cd Length: 127 Bit Score: 168.12 E-value: 6.99e-48

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1355 PDVVVNAANGDLRHLGGVAKAIDNFTGGKLTKRSkDYLKSNKSIAPGNAVLFENVLEHLSVLNAVGPRNGDSRVEGKLCN 1434
Cdd:cd21557     1 EDVVVNAANENLKHGGGVAGAIYKATGGAFQKES-DYIKKNGPLKVGTAVLLPGHGLAKNIIHVVGPRKRKGQDDQLLAA 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 240015189 1435 VYKAIAKCDGKILTPLISVGIFNVKLEVSLQCLLKTVTDRDLNVFVYT 1482
Cdd:cd21557    80 AYKAVNKEYGSVLTPLLSAGIFGVPPEQSLNALLDAVDTTDADVTVYC 127

alphaCoV_Nsp7

cd21826

alphacoronavirus non-structural protein 7; This model represents the non-structural protein 7 ...

3492-3574

3.73e-47

Pssm-ID: 409252 Cd Length: 83 Bit Score: 164.46 E-value: 3.73e-47

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3492 SKLTEMKCTNVVLLGLLSKMHVESNSKEWNYCVGLHNEINLCDDPEVVLEKLLALIAFFLSKHNTCDLSDLIDSYFENTT 3571
Cdd:cd21826     1 SKLTDIKCTNVVLLGCLSSMNVAANSKEWAYCVDLHNKINLCDDPEKAQEMLLALLAFFLSKQKDFGLDDLLDSYFDNNS 80


                  ...
gi 240015189 3572 ILQ 3574
Cdd:cd21826    81 ILQ 83

CoV_NSP7

pfam08716

Coronavirus replicase NSP7; NSP7 (non structural protein 7) has been implicated in viral RNA ...

3492-3574

7.06e-43

Coronavirus replicase NSP7; NSP7 (non structural protein 7) has been implicated in viral RNA replication and is predominantly alpha helical in structure. It forms a hexadecameric supercomplex with NSP8 that adopts a hollow cylinder-like structure. The dimensions of the central channel and positive electrostatic properties of the cylinder imply that it confers processivity on RNA-dependent RNA polymerase. NSP7 and NSP8 heterodimers play a role in the stabilization of NSP12 regions involved in RNA binding and are essential for a highly active NSP12 polymerase complex.

Pssm-ID: 285878 Cd Length: 83 Bit Score: 152.22 E-value: 7.06e-43

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  3492 SKLTEMKCTNVVLLGLLSKMHVESNSKEWNYCVGLHNEINLCDDPEVVLEKLLALIAFFLSKHNTCDLSDLIDSYFENTT 3571
Cdd:pfam08716    1 SKLTDVKCTNVVLLGLLQKLHVESNSKLWAYCVELHNEILLCDDPTEAFEKLLALLAVLLSKHSAVDLSDLCDSYLENRT 80


                   ...
gi 240015189  3572 ILQ 3574
Cdd:pfam08716   81 ILQ 83

CoV_peptidase

Coronavirus papain-like peptidase; This entry contains coronavirus cysteine endopeptidases ...

1496-1793

5.66e-39

Coronavirus papain-like peptidase; This entry contains coronavirus cysteine endopeptidases that belong to MEROPS peptidase family C16 and are required for proteolytic processing of the replicase polyprotein. All coronaviruses encode between one and two accessory cysteine proteinases that recognize and process one or two sites in the amino-terminal half of the replicase polyprotein during assembly of the viral replication complex. HCoV and TGEV encode two accessory proteinases, called coronavirus papain-like proteinase 1 and 2 (PL1-PRO and PL2-PRO). IBV and SARS encodes only one called PL-PRO. The structure of this protein has shown it adopts a fold similar that of de-ubiquitinating enzymes. The peptidase family C16 domain is about 260 amino acids in length. This domain is predicted to have an alpha-beta structural organization known as the papain-like fold. It consists of three alpha-helices and three strands of antiparallel beta-sheet.

Pssm-ID: 430171 Cd Length: 318 Bit Score: 149.75 E-value: 5.66e-39

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  1496 TIPVKVTEDTVNQKRVSVALDKTYGEQLkGTVVIKDKDVTNQLPSVSDAGEKVVKALDVDWNAYYGFPNAAAFSASSHDA 1575
Cdd:pfam08715    4 QITIYLTEDGVNYHSIVVKPGDSLGQQF-GQVYAKNKDLSGVFPADDVEDKEILYVPTTDWVEFYGFKSILEYYTLDASK 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  1576 Y-------KFDVVTHNNFIVHKQTDNNCWVNAICLALQRLKPTWKFPGVKSLWDVFLTRKTAGFVHMLYHISGLKKGQPG 1648
Cdd:pfam08715   83 YviylsalTKNVQYVDGFLILKWRDNNCWISSVIVALQAAKIRFKGQFLTEAWAKLLGGDPTDFVAWCYASCTAKVGDFG 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  1649 DAELTLHKLGELMVSDSIVTITHTTACDKCAKIENFTGPVVAAPLMI--------YGTDETCVHGVSVNVKVTSIRGTVA 1720
Cdd:pfam08715  163 DANWTLTNLAEHFDAEYTNAFLKKRVCCNCGIKSYELRGLEACIQVRatnldhfkTGYSNCCVCGANNTDEVIEASLPYL 242

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 240015189  1721 ITSLIG--PVVGDVIDATGYICYTGLNSRGHYtYYDNRNGLMVDAEKAYHFEKNLLQVTtaiaSNFVSNTPKNET 1793
Cdd:pfam08715  243 LLSATDgpAAVDCLEDGVGTVAFVGSTNSGHY-TYQTAKQAFYDGAKDRKFGKKSPYVT----AVYTRFAFKNET 312

CoV_NSP2_C

Coronavirus replicase NSP2, C-terminal; This entry corresponds to a presumed domain found at ...

731-879

1.29e-23

Pssm-ID: 465996 Cd Length: 156 Bit Score: 100.03 E-value: 1.29e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189   731 LSNVKIMLGNGVKVF--CDGCNSFAKRLTVSYSKLCDTARKDVEIGGLPFSTfktpASSFIDMKDAIYSVV--------E 800
Cdd:pfam19212    1 LKNAKFTVVNGGIVFvvPKKFKSLVGTLLDLLNKLFDSLVDTVKIAGVKFKA----GGTYYLFSNALVKVVsvklkgkkQ 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189   801 YG-----EAFSFKTANVPVTNSgTIKNDDwsdpILLEPADYVEP-KDNGDVIVIAGYTFYKDEDDHFYPYGSGMVVQKMY 874
Cdd:pfam19212   77 AGlkgakEATVFVGATVPVTPT-RVEVVT----VELEEVDYVPPpVVVGYVVVIDGYAFYKSGDEYYPASTDGVVVPPVF 151


                   ....*
gi 240015189   875 NKMGG 879
Cdd:pfam19212  152 KLKGG 156

alphaCoV_PLPro

alphacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...

1096-1279

6.23e-23

Pssm-ID: 409648 Cd Length: 289 Bit Score: 101.93 E-value: 6.23e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1096 FKTTDLNGKIILKQQDNNCWVNACCYQLQ------AFEFFNhDLWDDFKKGDVMPFVNFCYAALTLKQGDSGDAEHLLeT 1169
Cdd:cd21731    82 FESDIVNGKRVLKQSDNNCWVNAVCLQLQfakptfKSEGLQ-ALWNKFLTGDVAGFVHWLYWITGANKGDPGDAENTL-N 159

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1170 MLNDY--STAKVTLS--AKCGCGVKEIVLERTVFKLTPLRNEFKYGVCGDCKQINmCKFASVEGSGVFVHdrIEKQTPVS 1245
Cdd:cd21731   160 KLSKYlvSSGSVTVErtTGCDSCNSKRTVTTPVVNASVLRSGVDDGVCKHGVKVT-TRVVSVKGTVIITS--VGKPVVSD 236

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 240015189 1246 QFI-VTPTMHAVYTGTIQNGHYMIEDCIHDYCVDG 1279
Cdd:cd21731   237 ALLlLDGVSYTAFSGDVDNGHYTVYDKATGKVYDG 271

A1pp

smart00506

Appr-1"-p processing enzyme; Function determined by Martzen et al. Extended family detected by ...

1338-1467

6.63e-21

Appr-1"-p processing enzyme; Function determined by Martzen et al. Extended family detected by reciprocal PSI-BLAST searches (unpublished results, and Pehrson _ Fuji).

Pssm-ID: 214701 Cd Length: 133 Bit Score: 91.21 E-value: 6.63e-21

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189   1338 RISFYQGELDVLinflEPDVVVNAANGDLRHLGGVAKAIDNFTGGKLTKRSkdYLKSNK-SIAPGNAVLFEN-VLEHLSV 1415
Cdd:smart00506    1 ILKVVKGDITKP----RADAIVNAANSDGAHGGGVAGAIARAAGKALSKEE--VRKLAGgECPVGTAVVTEGgNLPAKYV 74

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|....*....
gi 240015189   1416 LNAVGPRNGDSRVEG--KLCNVYK-----AIAKCDGKILTPLISVGIFNVKLEVSLQCL 1467
Cdd:smart00506   75 IHAVGPRASGHSKEGfeLLENAYRnclelAIELGITSVALPLIGTGIYGVPKDRSAQAL 133

CoV_peptidase

Coronavirus papain-like peptidase; This entry contains coronavirus cysteine endopeptidases ...

1102-1311

9.64e-18

Pssm-ID: 430171 Cd Length: 318 Bit Score: 87.34 E-value: 9.64e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  1102 NGKIILKQQDNNCWVNACCYQLQAFEF-FN----HDLWDDFKKGDVMPFVNFCYAALTLKQGDSGDAE----HLLETMLN 1172
Cdd:pfam08715   98 DGFLILKWRDNNCWISSVIVALQAAKIrFKgqflTEAWAKLLGGDPTDFVAWCYASCTAKVGDFGDANwtltNLAEHFDA 177

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  1173 DYSTAKVTLSAKCGCGVKEIVL---ERTVFKLTPLRNEFK--YGVCGDCKQINMCKFASVEGSGVFVHdrIEKQTPVSQF 1247
Cdd:pfam08715  178 EYTNAFLKKRVCCNCGIKSYELrglEACIQVRATNLDHFKtgYSNCCVCGANNTDEVIEASLPYLLLS--ATDGPAAVDC 255

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 240015189  1248 IVTPTMHAVYTGTIQNGHYMiedciHDYCVDGMGLKPRKHKFYTSTLFLNANVMKEESKT-TIKP 1311
Cdd:pfam08715  256 LEDGVGTVAFVGSTNSGHYT-----YQTAKQAFYDGAKDRKFGKKSPYVTAVYTRFAFKNeTSLP 315

Macro

pfam01661

Macro domain; The Macro or A1pp domain is a module of about 180 amino acids which can bind ...

1359-1467

6.46e-10

Macro domain; The Macro or A1pp domain is a module of about 180 amino acids which can bind ADP-ribose (an NAD metabolite) or related ligands. Binding to ADP-ribose could be either covalent or non-covalent: in certain cases it is believed to bind non-covalently; while in other cases (such as Aprataxin) it appears to bind both non-covalently through a zinc finger motif, and covalently through a separate region of the protein. This domain is found in a number of otherwise unrelated proteins. It is found at the C-terminus of the macro-H2A histone protein 4 and also in the non-structural proteins of several types of ssRNA viruses such as NSP3 from alpha-viruses and coronaviruses. This domain is also found on its own in a family of proteins from bacteria, archaebacteria and eukaryotes. The 3D structure of the SARS-CoV Macro domain has a mixed alpha/beta fold consisting of a central seven-stranded twisted mixed beta sheet sandwiched between two alpha helices on one face, and three on the other. The final alpha-helix, located on the edge of the central beta-sheet, forms the C terminus of the protein. The crystal structure of AF1521 (a Macro domain-only protein from Archaeoglobus fulgidus) has also been reported and compared with other Macro domain containing proteins. Several Macro domain only proteins are shorter than AF1521, and appear to lack either the first strand of the beta-sheet or the C-terminal helix 5. Well conserved residues form a hydrophobic cleft and cluster around the AF1521-ADP-ribose binding site.

Pssm-ID: 460286 Cd Length: 116 Bit Score: 59.50 E-value: 6.46e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  1359 VNAANGDLRHLGGVAKAIDNFTGGKLTKRSKDYLKsnKSIAPGNAVLFEN-VLEHLSVLNAVGPR----NGDSRVEgKLC 1433
Cdd:pfam01661    1 VNAANSRLLGGGGVAGAIHRAAGPELLEECRELKK--GGCPTGEAVVTPGgNLPAKYVIHTVGPTwrhgGSHGEEE-LLE 77

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 240015189  1434 NVYK-AIAKCDGK----ILTPLISVGIFNVKLEVSLQCL 1467
Cdd:pfam01661   78 SCYRnALALAEELgiksIAFPAISTGIYGFPWEEAARIA 116

YmdB

COG2110

O-acetyl-ADP-ribose deacetylase (regulator of RNase III), contains Macro domain [Translation, ...

1339-1494

1.76e-08

O-acetyl-ADP-ribose deacetylase (regulator of RNase III), contains Macro domain [Translation, ribosomal structure and biogenesis];

Pssm-ID: 441713 Cd Length: 168 Bit Score: 56.72 E-value: 1.76e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1339 ISFYQG---ELDVlinflepDVVVNAANGDLRHLGGVAKAIDNFTGGKLTKRSKDYLKSNKsIAPGNAVLFEnvLEHLS- 1414
Cdd:COG2110     1 IEIVQGditELDV-------DAIVNAANSSLLGGGGVAGAIHRAAGPELLEECRRLCKQGG-CPTGEAVITP--AGNLPa 70

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1415 --VLNAVGP--RNGDSRVEGKLCNVYK-AIAKCDGKILT----PLISVGIFNVKLEVSLQCLLKTVTD--------RDLN 1477
Cdd:COG2110    71 kyVIHTVGPvwRGGGPSEEELLASCYRnSLELAEELGIRsiafPAIGTGVGGFPWEEAAPIAVETLRDfleehpslEEVR 150

                         170
                  ....*....|....*..
gi 240015189 1478 VFVYTDQEKVAIENFFN 1494
Cdd:COG2110   151 FVLFDEEDYEAYRRALA 167

PRK00431

ADP-ribose-binding protein;

1353-1473

8.00e-05

ADP-ribose-binding protein;

Pssm-ID: 234759 Cd Length: 177 Bit Score: 46.37 E-value: 8.00e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1353 LEPDVVVNAANGDLRHLGGVAKAIDNFTGGKLTKRSKDYLKSNKSIAPGNAVLFE-NVLEHLSVLNAVGP--RNGDSRVE 1429
Cdd:PRK00431   15 LEVDAIVNAANSSLLGGGGVDGAIHRAAGPEILEECRELRQQQGPCPTGEAVITSaGRLPAKYVIHTVGPvwRGGEDNEA 94

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 240015189 1430 GKLCNVYK-AIAKCDGKILT----PLISVGIFNVKLEVSLQCLLKTVTD 1473
Cdd:PRK00431   95 ELLASAYRnSLRLAAELGLRsiafPAISTGVYGYPLEDAARIAVKTVRE 143

Name

Accession

Description

Interval

E-value

TM_Y_alphaCoV_Nsp3_C

cd21712

C-terminus of alphacoronavirus non-structural protein 3, including transmembrane and Y domains; ...

1899-2399

0e+00

Pssm-ID: 409660 Cd Length: 501 Bit Score: 779.89 E-value: 0e+00

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1899 VRQLNKPALWRYAKLVLLLIALYHFFYLFVSIPLVHKLACSGSVQAYSNSSFVKSEVCGNSILCKACLASYDELADFDHL 1978
Cdd:cd21712     1 VIKLKKKKVWFFAKLLLLLYALYALLFMFVRFPPLNSSLCSGYVDGYANSSFVKSEVCGNSLLCKACLAGYDELSDFPHL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1979 QVSWDYKSDPLWNRVMQLSYFTFLAVFGNNYVRFCLMYFVTQYLNLWLSYFGYVKYSWFLHVINFESISVEFVIIVIVFE 2058
Cdd:cd21712    81 QVVWDHVSDPLFSNVLPLFYFAFLLIFGNNYVRCFLLYFVAQYINNWGVYFGYQDYSWFLHFVPFDSFSDEIVVIFIVVK 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2059 AVLALKHIFFPCNNPSCKTCSKIARQTRIPIQVVVNGSMKTVYVHANGTGKLCKKHNFYCKNCDSYGFDHTFICDEIVRD 2138
Cdd:cd21712   161 VLLFLKHVIFGCDKPSCKACSKSARLTRIPVQTIVNGSMKSFYVHANGGGKFCKKHNFFCVNCDSYGVGNTFINDEVARE 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2139 LSNSVKQTVYATDKSYQEVTKVECSDGFYRFYVGEEFTAYDYDVKHKKYSSQEVLKTMFLLDDFIVYSPSGSSLASVRNV 2218
Cdd:cd21712   241 LSNVVKTTVQPTGPAYIEVDKVEFSNGFYYLYSGDTFWRYNFDITEKKYSCKEVLKNCNLLDDFIVYNNNGSNVAQVKNA 320

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2219 CVYFSQLIGRPIKIVNSDLLEDLSVDFKGALFNAKKNVIKNSFNVDVSECKNLEECYKACNLDVTFSTFEMAINNAHRFG 2298
Cdd:cd21712   321 CVYFSQLLCKPIKLVDSALLSSLSVDFNGALHKAFVKVLKNSFNKDLSNCKTLEECKKALGLDVSDDEFESAVSNAHRYD 400

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2299 ILITDRSFNNFWPSKIKPGSSgVSAMDIGKCMTFDAKIVNAKVLTQRGKSVVWLSQDFSALSSTAQKVLVKTFVEEGVNF 2378
Cdd:cd21712   401 VLLTDRSFNNFVTSYAKPEEK-LSTHDIAVCMRAGAKVVNHNVLTKENVPIVWLAKDFSALSEEARKYIVKTTKAKGVNF 479

                         490       500
                  ....*....|....*....|.
gi 240015189 2379 SLTFNAVGSDEDLPYERFTES 2399
Cdd:cd21712   480 LLTFNDNRMTTTLPAVSIVSK 500

alphaCoV_Nsp2_HCoV-229E-like

cd21514

alphacoronavirus non-structural protein 2 (Nsp2), similar to HCoV-229E Nsp2 and related ...

110-715

0e+00

Pssm-ID: 394865 Cd Length: 503 Bit Score: 617.35 E-value: 0e+00

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  110 GAIYVDQYMCGADGKPVIEG---EFKDYFGDEDVIIYEGEEYHCAWLTVRDDKPLCQQTLLTIREIQYNLDIPHKLPNCA 186
Cdd:cd21514     1 NTVYVDQYMCGADGKPVLPEdewEFKDYFGDLDEIVINGITYVKAWDVERKDVPYEKQNLLSIESITYLSDIPHTLADGA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  187 IREVAPPVKKNSKVVLSEEYRKLYDIFGSPFMSNGDSLNKCFDSLHFIAATLKCPCGSESSGVGDWTGFKTACCGLHGKV 266
Cdd:cd21514    81 VLRVAKPPKKSKKVVLSEPYKKLYDAFGSPFVTNGSTLLEVVTKPVFIHALVKCKCGKESWTVGDWTGYKSSCCGVPCKP 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  267 KGVTLGAVKPGDAVVTSMSAGKGVKFFANSVLQYAGDVENVSVWKVIKTFTVNETVCTTDFEGELNdfikpESTSPVSCS 346
Cdd:cd21514   161 ICVVVGSVKPGDVVVTSLGAGSGVKYYNGMVLKHVCDVDGVSIWRVIKVQSVDGFVASGNFDEELH-----SELSLDACS 235

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  347 IKRafitgevddavhdciitgkldlstnlfgsanllfkKTPWFVQKCGAIFADAWKVVEELLCSLKLTYKQIYDVVASLC 426
Cdd:cd21514   236 FTN-----------------------------------DKPWFVRKLGDLFESAWDAFVAAVKSLKVTSKQLVDLVKALC 280

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  427 TSAFTIMDYKPVFVVSHSS-VKNLVDKCVKILVKAFDVFTQTITIAGveaKCFVLGSKYLLFNNALVKLVSVKILGKRQK 505
Cdd:cd21514   281 SAALTVVNGVIVFVADVPEkFKSAFEKFVSFVVGLFDLTCDTVKVAG---KKFKRVGDYVLLNNALVKLVSVKVKGVRQA 357

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  506 GLDSAFFVTNLIGATVNVTPQRTEAANISLNKVD-DVVTPGEGHIVIVGGMAFYKSEEYYFMMASPDSVLVNNVFKAarv 584
Cdd:cd21514   358 GLKTAQYATVVVGKTTKVTSSRVEVATVNLVLVDeDVPLPGEGYTVVIGGQAFFCSGGYYRLMADPDEVLETPVFKA--- 434

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  585 psynivydvddntkskmvvkigtsfdfdgdldaaiakvndlliefrqeklcfralkdgenilveayfkkYKMPVCLKNHV 664
Cdd:cd21514   435 ---------------------------------------------------------------------FKAPSYIKDEV 445

                         570       580       590       600       610
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 240015189  665 GLWDIVRRDSDKKGFLDTFNHLNDLEDVKETK-------IQAIKNILCPDLLLELDFG 715
Cdd:cd21514   446 EFVDLCEKYVGEPGFDEFYVAAHEALDLDQFEvalfsfdKVDEKEPECPELLLEIDGG 503

CoV_NSP3_C

pfam19218

Coronavirus replicase NSP3, C-terminal; This family represents the C-terminal region of ...

1935-2383

0e+00

Pssm-ID: 466002 Cd Length: 463 Bit Score: 616.27 E-value: 0e+00

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  1935 KLACSGSVQAYSNSSFVKSEVCGNSILCKACLASYDELADFDHLQVSWDYKSDPLWNRVMQLSYFTF-----LAVFGNNY 2009
Cdd:pfam19218    1 GYPCDGYVDGYSNSSFNKSDYCNGSILCKACLSGYDSLHDYPHLKVVQQPVKDPLFVDVTPLFYFAIelfvaLALFGGTF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  2010 VRFCLMYFVTQYLNLWLSYFGYVKYSWFLHVINFESISVEFVIIVIVFEAVLALKHIFFPCNNPSCKTCSKIARQTRIPI 2089
Cdd:pfam19218   81 VRVFLLYFLQQYVNFFGVYLGLQDYSWFLTLIPFDSFLREYVVLFYVIKLYRFLKHVVFGCKKPSCLACSKSARLTRVPV 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  2090 QVVVNGSMKTVYVHANGTGKLCKKHNFYCKNCDSYGFDHTFICDEIVRDLSNSVKQTVYATDKSYQEVTKVECSDGFYRF 2169
Cdd:pfam19218  161 STVVNGSKKSFYVNANGGTKFCKKHNFFCKNCDSYGPGNTFINDEVAEDLSNVTKRSVKPTDPAYYEVDKVEFQNGFYYL 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  2170 YVGEEFTAYDYDVKHKKYSSQEVLKTMFL----LDDFIVYSPSGSSLASVRNVCVYFSQLIGRPIKIVNSDLLEDL--SV 2243
Cdd:pfam19218  241 YSGREFWRYYFDVTVSKYSDKEVLKNCNIkgypLDDFIVYNSNGSNLAQAKNACVYYSQLLCKPIKLVDSNLLSSLgdSV 320

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  2244 DFKGALFNAKKNVIKNSFNVDVSECKNLEECYKACNLDVTFSTFEMAINNAHRFGILITDRSFNNFWPSKIKPGSSgVSA 2323
Cdd:pfam19218  321 DVNGALHDAFVEVLLNSFNVDLSKCKTLIECKKDLGSDVDTDSFVNAVLNAHRYDVLLTDDSFNNFVPTYAKPEDS-LST 399

                          410       420       430       440       450       460
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  2324 MDIGKCMTFDAKIVNAKVLTQRGKSVVWLSQDFSALSSTAQKVLVKTFVEEGVNFSLTFN 2383
Cdd:pfam19218  400 HDLAVCIRFGAKIVNHNVLKKENVPVVWSADDFLKLSEEARKYIVKTAKKKGVTFMLTFN 459

alphaCoV_Nsp5_Mpro

cd21665

alphacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily ...

2898-3193

0e+00

Pssm-ID: 394886 Cd Length: 296 Bit Score: 589.26 E-value: 0e+00

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2898 LRKMAQPSGIVEPCIVRVAYGNNVLNGLWIGDEVICPRHVIASDTSRVINYENELSSVRLHNFSIAKNNVFLGVVSVKYK 2977
Cdd:cd21665     1 LRKMAQPSGVVEKCVVRVSYGNMVLNGLWLGDTVYCPRHVIASDTTSTIDYDHEYSLMRLHNFSISVGNVFLGVVGVTMR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2978 GVNLVLKVNQVNPNTPEHKFKSVKPGESFNILACYEGCPGSVYGVNMRSQGTIKGSFIAGTCGSVGYVLENGTLYFVYMH 3057
Cdd:cd21665    81 GALLVIKVNQNNVNTPKYTFRTLKPGDSFNILACYDGVPSGVYGVNMRTNYTIKGSFINGACGSPGYNLNNGTVEFCYMH 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3058 HLELGNGSHVGSNLEGEMYGGYEDQPSMQLEGTNVMSSDNVVAFLYAALINGERWFVTNASMSLESYNAWAKTNSFTEIV 3137
Cdd:cd21665   161 QLELGSGCHVGSDLDGVMYGGYEDQPTLQVEGANVLVTENVVAFLYAALLNGCNWWLSSDRVTVEAFNEWAVANGFTTVS 240

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 240015189 3138 STDAFNMLAAKTGYSVEKLLECIVRLNKGFGGRTILSYGSLCDEFTPTEVIRQMYG 3193
Cdd:cd21665   241 STDCFSILAAKTGVDVERLLAAIQRLSKGFGGKTILGYTSLTDEFTLSEVIKQMYG 296

Peptidase_C30

pfam05409

Coronavirus endopeptidase C30; This Coronavirus (CoV) domain, peptidase C30, is also known as ...

2924-3197

7.73e-168

Pssm-ID: 398852 Cd Length: 274 Bit Score: 518.15 E-value: 7.73e-168

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  2924 GLWIGDEVICPRHVIASDTSRVINYENELSSVRLHNFSIAKNNVFLGVVSVKYKGVNLVLKVNQVNPNTPEHKFKSVKPG 3003
Cdd:pfam05409    1 GLWLGDTVYCPRHVIGSFTGMLPQYEHLLSIARNHDFCVVSGGVQLTVVSAKMQGAILVLKVHTNNPNTPKYKFVRLKPG 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  3004 ESFNILACYEGCPGSVYGVNMRSQGTIKGSFIAGTCGSVGYVLENGTLYFVYMHHLELGNGSHVGSNLEGEMYGGYEDQP 3083
Cdd:pfam05409   81 ESFTILAAYDGCPQGVYHVTMRSNHTIKGSFLNGACGSVGYNLKGGTVCFVYMHHLELPNGSHTGTDLEGVFYGPYVDEE 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  3084 SMQLEGTNVMSSDNVVAFLYAALINGERWFVTNASMSLESYNAWAKTNSFTEIVSTDAFNMLAAKTGYSVEKLLECIVRL 3163
Cdd:pfam05409  161 VAQLEGTDQTYTDNVVAWLYAAIINGPRWFLASTTVSLEDFNAWAMTNGFTPFPCEDAILGLAAKTGVSVERLLAAIKVL 240

                          250       260       270
                   ....*....|....*....|....*....|....
gi 240015189  3164 NKGFGGRTILSYGSLCDEFTPTEVIRQMYGVNLQ 3197
Cdd:pfam05409  241 NNGFGGRTILGSPSLEDEFTPEDVYNQMAGVTLQ 274

cv_Nsp4_TM

cd21473

coronavirus non-structural protein 4 (Nsp4) transmembrane domain; Nsp4 may be involved in ...

2419-2792

1.48e-161

Pssm-ID: 394836 Cd Length: 376 Bit Score: 504.82 E-value: 1.48e-161

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2419 FWCLVFFIIIYGLCSVYSVATQSYIdSAEGYDYMVIKNGVVQPFDDSINCVHNTYKGFAVWFKAKYGFIPTFDKSCPIVL 2498
Cdd:cd21473     2 LWLLLAAILLYAFLPSYSVFTVTVS-SFPGYDFKVIENGVLRDIRSTDTCFANKFVNFDSWYQAKYGSVPTNSKSCPIVV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2499 GTVFDLGNMrpIPDVPAYVALVGRSLVFAINAA-FGVTNVCYDHTGAAVSKNSYFDTCVFNSACTTLAGLGGTVVYCAKQ 2577
Cdd:cd21473    81 GVIDDVRGS--VPGVPAGVLLVGKTLVHFVQTVfFGDTVVCYTPDGVITYDSFYTSACVFNSACTYLTGLGGRQLYCYDT 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2578 GLVEGAKLYSELMPDYYYEHASGNMVKIPAIVRGFGLRFVKTQATTYCRVGECIESQAGFCFGGDNWFVYDKEF-GDGYI 2656
Cdd:cd21473   159 GLVEGAKLYSDLLPHVRYKLVDGNYIKFPEVILEGGPRIVRTLATTYCRVGECEDSKAGVCVSFDGFWVYNNDYyGPGVY 238

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2657 CGSSALGFFKNVFALFNSNMSVVATSGAMLANIIIACLAIAVCYGVLKFKKIFGDCTLLVVMIIVTLVVNNVSYFVTQNT 2736
Cdd:cd21473   239 CGDGLFDLLTNLLSGFFQPVSVFALSGQLLFNTIVAILAVLACYYVQKFKRAFGDMSVVVVTVVAAALVNNVLYVVTQNP 318

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 240015189 2737 LFMIVYAIIYYFTTRKFAY--PGILDAGFIIAYMNMAPWYVLVLYIMVFLYDSLPSLF 2792
Cdd:cd21473   319 LLMIVYAVLYFYATLYLTYerAWIMHLGWVVAYGPIAPWWLLALYVVAVLYDYLPWFF 376

CoV_NSP4_N

pfam19217

Coronavirus replicase NSP4, N-terminal; This is the N-terminal domain of the coronavirus ...

2430-2777

1.07e-144

Pssm-ID: 466001 Cd Length: 351 Bit Score: 455.19 E-value: 1.07e-144

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  2430 GLCSVYSVATQSYIDSAEGYDYMVIKNGVVQPFDDSINCVHNTYKGFAVWFKAKYGFiPTFDKSCPIVLGTVF-DLGNMr 2508
Cdd:pfam19217    1 YALSPTFFNTVVYFVSDPVYDFKVIENGVLRDFRSTDTCFHNKFDNFDSWHQAKFGS-PTNSRSCPIVVGVVDeVVGRV- 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  2509 pIPDVPAYVALV-GRSLVFAINAAFGVTNVCYDHTGAAVSKNSYFDTCVFNSACTTLAGLGGT-VVYCAKQGLVEGAKLY 2586
Cdd:pfam19217   79 -VPGVPAGVALVgGTILHFVTRVFFGAGNVCYTPSGVVTYESFSASACVFNSACTTLTGLGGTrVLYCYDDGLVEGAKLY 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  2587 SELMPDYYYEHASGNMVKIPAIVRGFGLRFVKTQATTYCRVGECIESQAGFCFGGDNWFVYDKEFGDGYICGSSALGFFK 2666
Cdd:pfam19217  158 SDLVPHVRYKLVDGNYVKLPEVLFRGGFRIVRTLATTYCRVGECEDSKAGVCVGFDRSFVYNNDFGPGVYCGSGFLSLLT 237

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  2667 NVFALFNSNMSVVATSGAMLANIIIACLAIAVCYGVLKFKKIFGDCTLLVVMIIVTLVVNNVSYFVTQ-NTLFMIVYAII 2745
Cdd:pfam19217  238 NVFSGFNTPISVFALTGQLMFNCVVALIAVCVCYYVLKFKRAFGDYSTGVLTVVLATLVNNLSYFVTQvNPVLMIVYAVL 317

                          330       340       350
                   ....*....|....*....|....*....|....
gi 240015189  2746 YYFTTRKFAYP--GILDAGFIIAYMNMAPWYVLV 2777
Cdd:pfam19217  318 YFYATLYVTPEyaWIWHLGFLVAYVPLAPWWVLL 351

CoV_Nsp5_Mpro

cd21646

coronavirus non-structural protein 5, also called Main protease (Mpro); This family contains ...

2899-3190

2.24e-141

coronavirus non-structural protein 5, also called Main protease (Mpro); This family contains the coronavirus (CoV) non-structural protein 5 (Nsp5) also called the Main protease (Mpro), or 3C-like protease (3CLpro). CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Mpro/Nsp5 is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. These enzymes belong to the MEROPS peptidase C30 family, where the active site residues His and Cys form a catalytic dyad. The structures of Mpro/Nsp5 consist of three domains with the first two containing anti-parallel beta barrels and the third consisting of an arrangement of alpha-helices. The catalytic residues are found in a cleft between the first two domains. Mpro/Nsp5 requires a Gln residue in the P1 position of the substrate and space for only small amino-acid residues such as Gly, Ala, or Ser in the P1' position; since there is no known human protease with a specificity for Gln at the cleavage site of the substrate, these viral proteases are suitable targets for the development of antiviral drugs.

Pssm-ID: 394885 Cd Length: 292 Bit Score: 443.40 E-value: 2.24e-141

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2899 RKMAQPSGIVEPCIVRVAYGNNVLNGLWIGDEVICPRHVIASDTSRVINYENELSSVRLHNFSIAKNNVFLGVVSVKYKG 2978
Cdd:cd21646     1 KKMAQPSGKVERCMVSVTYGSTTLNGLWLDDTVYCPRHVICKSTTSGPDYDDLLSRARNHNFSVQSGGVQLRVVGVTMQG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2979 VNLVLKVNQVNPNTPEHKFKSVKPGESFNILACYEGCPGSVYGVNMRSQGTIKGSFIAGTCGSVGYVLENGTLYFVYMHH 3058
Cdd:cd21646    81 ALLRLKVDTSNPHTPKYKFVTVKPGDSFTILACYNGSPSGVYGVNMRSNYTIKGSFLNGACGSVGYNIDGGTVEFCYMHH 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3059 LELGNGSHVGSNLEGEMYGGYEDQPSMQLEGTNVMSSDNVVAFLYAALINGERWFVTNASMSLESYNAWAKTNSFTEIVS 3138
Cdd:cd21646   161 LELPNGCHTGTDLTGKFYGPYVDQQVAQVEGADTLITDNVVAWLYAAIINGDRWWLNSSRTTVNDFNEWAMANGFTPVSQ 240

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 240015189 3139 TDAFNMLAAKTGYSVEKLLECIVRLNKGFGGRTILSYGSLCDEFTPTEVIRQ 3190
Cdd:cd21646   241 VDCLSILAAKTGVSVERLLAAIQQLHQNFGGKQILGSTSLEDEFTPEDVVRQ 292

alphaCoV-Nsp6

cd21558

alphacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host ...

3182-3491

2.82e-136

Pssm-ID: 394844 Cd Length: 293 Bit Score: 428.54 E-value: 2.82e-136

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3182 FTPTEVIRQMYGVNLQSGKVKSLFYPVMTAIAILFAFWLEFFMYTPFTWINPAFVSVILAITTLVSAVLVVGIKHKMLFF 3261
Cdd:cd21558     1 FTTSEVIKQMYGVNLQSGKVKSAFKNVLLVGVFLFMFWSELLMYTSFFWINPGLVTPVFLVLVLVSLLLTLFLKHKMLFL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3262 MSFVMPSVILATAHNVVWDMtYYESLQALVENVNTTFLPVDMQGVMLALFCVVVFVTYTIRFFTCKQSWFSLFVTTVFVM 3341
Cdd:cd21558    81 QTFLLPSVIVTAFYNLAWDY-YVTAVLAEYFDYHVSLMSFDIQGVLNIFVCLFVFFLHTYRFVTSGTSWFTYVVSLVFVL 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3342 FNIVKLLGmigepwtddhillcLVNMLTMLISLTTKDWFVVFVSYKVAYYIVVyvMHPAFVQDFGFIKCVSIIYMACGYL 3421
Cdd:cd21558   160 YNYFYGND--------------YLSLLMMVLSSITNNWYVGAIAYKLAYYIVY--VPPSLVADFGTVKAVMLVYVALGYL 223

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3422 FCCYYGILYWVNRFTCMTCGVYQFTVSPAELKYMTANNLSAPKTAYDAMILSVKLMGIGGERNIKISTVQ 3491
Cdd:cd21558   224 CCVYYGILYWINRFTKLTLGVYDFKVSAAEFKYMVANGLKAPTGVFDALLLSFKLIGIGGERTIKISTVQ 293

alphaCoV_PLPro

alphacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...

1495-1781

9.60e-134

Pssm-ID: 409648 Cd Length: 289 Bit Score: 421.26 E-value: 9.60e-134

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1495 GTIPVKVTEDTVNQKRVSVALDKTYGEQLkGTVVIKDKDVTNQ-LPSVSDAGEKVvkALDVDWNAYYGFPNAAAFSASSH 1573
Cdd:cd21731     1 KSVVVKVTEDGRNVKDVVVDTDKTFGEQL-GVCSVNDKDVTGVvPPDDSDKVVSV--APDVDWDSHYGFPNAAVFHTLDH 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1574 DAYKFDVVTHNNFIVHKQTDNNCWVNAICLALQRLKPTWKFPGVKSLWDVFLTRKTAGFVHMLYHISGLKKGQPGDAELT 1653
Cdd:cd21731    78 SAYAFESDIVNGKRVLKQSDNNCWVNAVCLQLQFAKPTFKSEGLQALWNKFLTGDVAGFVHWLYWITGANKGDPGDAENT 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1654 LHKLGELMVSDSIVTITHTTACDKCAKIENFTGPVV-AAPLMIYGTDETCVHGVSVNVKVTSIRGTVAITSLIGPVVGDV 1732
Cdd:cd21731   158 LNKLSKYLVSSGSVTVERTTGCDSCNSKRTVTTPVVnASVLRSGVDDGVCKHGVKVTTRVVSVKGTVIITSVGKPVVSDA 237

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 240015189 1733 ---IDATGYICYTGLNSRGHYTYYDNRNGLMVDAEKAYHFEKNLLQVTTAIA 1781
Cdd:cd21731   238 lllLDGVSYTAFSGDVDNGHYTVYDKATGKVYDGDKTVSFKLDLLSVTSVVV 289

alphaCoV_Nsp8

cd21830

alphacoronavirus non-structural protein 8; This model represents the non-structural protein 8 ...

3575-3769

2.24e-126

Pssm-ID: 409257 Cd Length: 195 Bit Score: 395.95 E-value: 2.24e-126

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3575 SVASAYAALPSWIAYEKARADLEEAKKNDVSPQLLKQLTKACNIAKSEFEREVSVQKKLDKMAEQAAASMYKEARAVDRK 3654
Cdd:cd21830     1 SVASTFANMPSFIAYETARQDYEDAVKNGSSPQLIKQLKKAMNIAKSEFDREASVQRKLDRMAEQAAAQMYKEARAVNRK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3655 SKIVSAMHSLLFGMLKKLDMSSVNTIIEQARNGVLPLSIIPAASATRLIVVTPNLEVLSKVRQENNVHYAGAIWSIVEVK 3734
Cdd:cd21830    81 SKVISAMHSLLFGMLRRLDMSSVDTILNLAKDGVVPLSIIPAASATRLVVVVPDLESFSKIRRDGCVHYAGVVWTIVDIK 160

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 240015189 3735 DANGSQVHLKEVTAANELNITWPLSITCERTTKLQ 3769
Cdd:cd21830   161 DNDGKVVHLKEVTAANEESLAWPLHLNCERIVKLQ 195

betaCoV_Nsp5_Mpro

cd21666

betacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily ...

2899-3191

6.29e-113

betacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily contains the coronavirus (CoV) non-structural protein 5 (Nsp5) also called the Main protease (Mpro), or 3C-like protease (3CLpro), found in betacoronaviruses. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Mpro/Nsp5 is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. These enzymes belong to the MEROPS peptidase C30 family, where the active site residues His and Cys form a catalytic dyad. The structures of Mpro/Nsp5 consist of three domains with the first two containing anti-parallel beta barrels and the third consisting of an arrangement of alpha-helices. The catalytic residues are found in a cleft between the first two domains. Mpro requires a Gln residue in the P1 position of the substrate and space for only small amino-acid residues such as Gly, Ala, or Ser in the P1' position; since there is no known human protease with a specificity for Gln at the cleavage site of the substrate, these viral proteases are suitable targets for the development of antiviral drugs.

Pssm-ID: 394887 Cd Length: 297 Bit Score: 361.72 E-value: 6.29e-113

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2899 RKMAQPSGIVEPCIVRVAYGNNVLNGLWIGDEVICPRHVIASDTSRVI-NYENELSSVRLHNFSIAKNNVFLGVVSVKYK 2977
Cdd:cd21666     1 RKMAFPSGKVEGCMVQVTCGTMTLNGLWLDDTVYCPRHVICTAEDMLNpNYEDLLIRKTNHSFLVQAGNVQLRVIGHSMQ 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2978 GVNLVLKVNQVNPNTPEHKFKSVKPGESFNILACYEGCPGSVYGVNMRSQGTIKGSFIAGTCGSVGYVLENGTLYFVYMH 3057
Cdd:cd21666    81 GCLLRLTVDTSNPKTPKYKFVRVKPGQTFSVLACYNGSPSGVYQCAMRPNHTIKGSFLCGSCGSVGYNIDGDCVSFCYMH 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3058 HLELGNGSHVGSNLEGEMYGGYEDQPSMQLEGTNVMSSDNVVAFLYAALINGERWFVTNASMSLESYNAWAKTNSFTEIV 3137
Cdd:cd21666   161 QMELPTGVHTGTDLEGKFYGPFVDRQTAQAAGTDTTITLNVLAWLYAAVLNGDRWFVNRFTTTLNDFNLWAMKYNYEPLT 240

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 240015189 3138 --STDAFNMLAAKTGYSVEKLLECIVRLNKGFG-GRTILSYGSLCDEFTPTEVIRQM 3191
Cdd:cd21666   241 qdHVDILDPLAAQTGIAVEDMLAALKELLQGGMqGRTILGSTILEDEFTPFDVVRQC 297

CoV_NSP8

pfam08717

Coronavirus replicase NSP8; Viral NSP8 (non structural protein 8) forms a hexadecameric ...

3575-3765

1.17e-109

Pssm-ID: 400866 Cd Length: 197 Bit Score: 347.99 E-value: 1.17e-109

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  3575 SVASAYAALPSWIAYEKARADLEEAKKNDVSPQLLKQLTKACNIAKSEFEREVSVQKKLDKMAEQAAASMYKEARAVDRK 3654
Cdd:pfam08717    1 SVASEFSSLPSYAAYETAKEAYEEAVANGSSQQVLKQLKKACNIAKSEFDRDAAVQKKLEKMAEQAMTQMYKEARAVDRK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  3655 SKIVSAMHSLLFGMLKKLDMSSVNTIIEQARNGVLPLSIIPAASATRLIVVTPNLEVLSKVRQENNVHYAGAIWSIVEVK 3734
Cdd:pfam08717   81 SKVVSAMHTLLFSMLRKLDNSALNTIINNARNGVVPLNIIPATTAAKLTVVVPDYETFVKVVDGNTVTYAGAVWEIQEVK 160

                          170       180       190
                   ....*....|....*....|....*....|.
gi 240015189  3735 DANGSQVHLKEVTAANELNITWPLSITCERT 3765
Cdd:pfam08717  161 DADGKIVHLKEITMDNSPNLAWPLIVTAERA 191

CoV_Nsp8

cd21816

Coronavirus non-structural protein 8; This model represents the non-structural protein 8 (Nsp8) ...

3578-3769

6.24e-99

Coronavirus non-structural protein 8; This model represents the non-structural protein 8 (Nsp8) of alpha-, beta-, gamma- and deltacoronaviruses, including highly pathogenic betacoronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9, and Nsp10 form functional complexes with CoV core enzymes and thereby stimulate replication. Most importantly, a complex of Nsp8 with Nsp7 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the genes encoding Nsp8 and Nsp7 have been shown to delay virus growth. Nsp8 and Nsp7 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp8 with Nsp7 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp8 has a novel 'golf-club' fold composed of an N-terminal 'shaft' domain and a C-terminal 'head' domain. The shaft domain contains three helices, one of which is very long, while the head domain contains another three helices and seven beta-strands, forming an alpha/beta fold. SARS-CoV Nsp8 forms a 8:8 hexadecameric supercomplex with Nsp7 that adopts a hollow cylinder-like structure with a large central channel and positive electrostatic properties in the cylinder, while Feline infectious peritonitis virus Nsp8 forms a 1:2 heterotrimer with Nsp7. Regardless of their oligomeric structure, the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to the template length.

Pssm-ID: 409256 Cd Length: 194 Bit Score: 317.16 E-value: 6.24e-99

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3578 SAYAALPSWIAYEKARADLEEAKKNDVSPQLLKQLTKACNIAKSEFEREVSVQKKLDKMAEQAAASMYKEARAVDRKSKI 3657
Cdd:cd21816     1 SEFSHLPSYAAYATAQAAYEQAVKNGDSPQELKKLTKALNIAKSEFDRDAAVQKKLEKMADQAMTSMYKEARAEDRRAKI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3658 VSAMHSLLFGMLKKLDMSSVNTIIEQARNGVLPLSIIPAASATRLIVVTPNLEVLSKVRQENNVHYAGAIWSIVEVKDAN 3737
Cdd:cd21816    81 TSAMHALLFSMLKKLDSDAVNNIFEQARDGVVPLNIIPLTTANKLMVVIPDYETYKKTVDGNTFTYAGALWSIVTVVDAD 160

                         170       180       190
                  ....*....|....*....|....*....|....
gi 240015189 3738 GSQVHLKEVTAANELNITWPLSITCERT--TKLQ 3769
Cdd:cd21816   161 GKIVHLSEINMDNSPNIAWPLIVTCLRAgaVKLQ 194

CoV_NSP6

pfam19213

Coronavirus replicase NSP6; This entry represents proteins found in Coronaviruses and includes ...

3222-3491

6.61e-99

Pssm-ID: 465997 Cd Length: 260 Bit Score: 319.97 E-value: 6.61e-99

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  3222 FFMYTPFTWINPAFVSVILAITTLVSAVLVVGIKHKMLFFMSFVMPSVILATAHNVVWDMtYYESLQALVENVNTTFLPV 3301
Cdd:pfam19213    1 LLMYTALYWLPPNLITPVLPVLTCVSAILTLFIKHKVLFLTTFLLPSVVVMAYYNFTWDY-YPNSFLRTVYDYHFSLTSF 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  3302 DMQGVMLALFCVVVFVTYTIRFFTCKQSWFSLFVTTVFVMFNIVKLLGMIGEPWTddhillclVNMLTMLISLTTKDWFV 3381
Cdd:pfam19213   80 DLQGYFNIASCVFVNVLHTYRFVRSKYSIATYLVSLVVSVYMYVIGYALLTATDV--------LSLLFMVLSLLTSYWYV 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  3382 VFVSYKVAYYIVVYvMHPAFVQDFGFIKCVSIIYMACGYLFCCYYGILYWVNRFTCMTCGVYQFTVSPAELKYMTANNLS 3461
Cdd:pfam19213  152 GAIAYKLAKYIVVY-VPPSLIAVFGDIKVVLLVYVCIGYVCCVYFGILYWINRFTKLTLGVYDFKVSAAEFKYMVANGLS 230

                          250       260       270
                   ....*....|....*....|....*....|
gi 240015189  3462 APKTAYDAMILSVKLMGIGGERNIKISTVQ 3491
Cdd:pfam19213  231 APRNVFEALILNFKLLGIGGNRTIKISTVQ 260

CoV_NSP2_N

pfam19211

Coronavirus replicase NSP2, N-terminal; This entry corresponds to the N-terminal region of ...

111-310

4.01e-95

Pssm-ID: 465995 [Multi-domain] Cd Length: 204 Bit Score: 306.58 E-value: 4.01e-95

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189   111 AIYVDQYMCGADGKPVIEG---EFKDYFGDEDVIIYEGEEYHCAWLTVRDDKPLCQQTLLTIREIQYNLDIPHKLPNCAI 187
Cdd:pfam19211    2 VIPVDQYMCGADGKPVLPEdtwCFKDYFGDDGEIVLNGGTYRKAWKVVRKNVPYPKQSLFTINSITYLGDIPHVLPNGAV 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189   188 REVAPPVKKNSKVVLSEEYRKLYDIFGSPFMSNGDSLNKCFDSLHFIAATLKCPCGSESSGVGDWTGFKTACCGLHGKVK 267
Cdd:pfam19211   82 LHVAPRVKKSKKVVLSEKYKSLYDTYGSPFVTNGSTLLEIVPKPVFHHALVKCSCGRESWTVGDWSGFKCLCCGVYGKPI 161

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|...
gi 240015189   268 GVTLGAVKPGDAVVTSMSAGKGVKFFANSVLQYAGDVENVSVW 310
Cdd:pfam19211  162 CVSAGDVKPGDVLITKAPVGRGKKFFGGAVLKYVGCVEGVSVW 204

alpha_betaCoV_Nsp10

cd21901

alphacoronavirus and betacoronavirus non-structural protein 10; This model represents the ...

3881-4010

5.81e-93

Pssm-ID: 409326 Cd Length: 130 Bit Score: 297.27 E-value: 5.81e-93

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3881 AGKPTEHPSNSGLLTLCAFAPDPAKAYVDAVKRGMQPVTNCVKMLSNGAGNGMAVTNGVESNTQQDSYGGASVCIYCRCH 3960
Cdd:cd21901     1 AGKQTEVASNSSLLTLCAFAVDPAKTYLDAVKSGGKPVGNCVKMLTNGTGTGQAITVKPEANTNQDSYGGASVCLYCRAH 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 240015189 3961 VEHPAIDGLCRFKGKFVQVPTGTQDPIRFCIENEICVVCGCWLNNGCMCD 4010
Cdd:cd21901    81 VEHPDMDGVCKLKGKYVQVPLGTNDPVRFCLENDVCKVCGCWLGNGCSCD 130

gammaCoV_Nsp5_Mpro

cd21667

gammacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily ...

2897-3197

4.37e-81

gammacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily contains the coronavirus (CoV) non-structural protein 5 (Nsp5) also called the Main protease (Mpro), or 3C-like protease (3CLpro), found in gammacoronaviruses. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Mpro/Nsp5 is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. These enzymes belong to the MEROPS peptidase C30 family, where the active site residues His and Cys form a catalytic dyad. The structures of Mpro/Nsp5 consist of three domains with the first two containing anti-parallel beta barrels and the third consisting of an arrangement of alpha-helices. The catalytic residues are found in a cleft between the first two domains. Mpro/Nsp5 requires a Gln residue in the P1 position of the substrate and space for only small amino-acid residues such as Gly, Ala, or Ser in the P1' position; since there is no known human protease with a specificity for Gln at the cleavage site of the substrate, these viral proteases are suitable targets for the development of antiviral drugs.

Pssm-ID: 394888 Cd Length: 306 Bit Score: 270.89 E-value: 4.37e-81

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2897 GLRKMAQPSGIVEPCIVRVAYGNNVLNGLWIGDEVICPRHVIASDTSRviNYENELSSVRLHNFSIAKNN-VFLGVVSVK 2975
Cdd:cd21667     1 GFKKLVSPSSAVEKCIVSVSYRGNNLNGLWLGDSIYCPRHVLGKFSGD--QWQDVLNLANNHEFEVVTQNgVTLNVVSRR 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2976 YKGVNLVLKVNQVNPNTPEHKFKSVKPGESFNILACYEGCPGSVYGVNMRSQGTIKGSFIAGTCGSVGYVLENGTLYFVY 3055
Cdd:cd21667    79 LKGAVLILQTAVANANTPKYKFVKANCGDSFTIACSYGGTVVGLYPVTMRSNGTIRASFLAGACGSVGFNIEKGVVNFFY 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3056 MHHLELGNGSHVGSNLEGEMYGGYEDQPSMQLEGTNVMSSDNVVAFLYAALINGE-------RWfVTNASMSLESYNAWA 3128
Cdd:cd21667   159 MHHLELPNALHTGTDLMGEFYGGYVDEEVAQRVPPDNLVTNNIVAWLYAAIISVKessfslpKW-LESTTVSVEDYNKWA 237

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 240015189 3129 KTNSFTEIVSTDAFNMLAAKTGYSVEKLLECIVRLNKGFGGRTILSYGSLCDEFTPTEVIRQMYGVNLQ 3197
Cdd:cd21667   238 SDNGFTPFSTSTAITKLSAITGVDVCKLLRTIMVKSAQWGSDPILGQYNFEDELTPESVFNQVGGVRLQ 306

TM_Y_CoV_Nsp3_C

cd21686

C-terminus of coronavirus non-structural protein 3, including transmembrane and Y domains; ...

1908-2383

5.01e-78

C-terminus of coronavirus non-structural protein 3, including transmembrane and Y domains; This model represents the C-terminus of non-structural protein 3 (Nsp3) from alpha-, beta-, gamma-, and deltacoronavirus, including highly pathogenic betacoronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. This conserved C-terminus includes two transmembrane (TM) regions TM1 and TM2, an ectodomain (3Ecto) between the TM1 and TM2 that is glycosylated and located on the lumenal side of the ER, an amphiphatic region (AH1) that is not membrane-spanning, and a large Y domain of approximately 370 residues. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. In SARS-CoV and murine hepatitis virus (MHV), the TM1, 3Ecto and TM2 domains are important for the papain-like protease (PL2pro) domain to process Nsp3-Nsp4 cleavage. It has also been shown that the interaction of 3Ecto with the lumenal loop of Nsp4 is essential for ER rearrangements in cells infected with SARS-CoV or MHV. The Y domain, located at the cytosolic side of the ER, consists of the Y1 and CoV-Y subdomains, which are conserved in nidovirus and coronavirus, respectively. Functional information about the Y domain is limited; it has been shown that Nsp3 binding to Nsp4 is less efficient without the Y domain.

Pssm-ID: 409657 Cd Length: 476 Bit Score: 268.68 E-value: 5.01e-78

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1908 WRYAKLVLL------LIALYHFFYLFVSIPLVHKLACSGSVQAYSNSSFV-KSEVCGNSILCKACLASYDELADFDHLQV 1980
Cdd:cd21686     1 LFYLASVLFkslapfLLLPAVLYLLNSGYTLGTGSYCKTYWPGYYNSTQHdYNSYCAGDLVCQVCLDGQDSLHLYPHLRV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1981 ------SWDYK----SDPLWNRVMQLSYFTFLAVFGNNYVRFCLMYfvtqylnlwlsyfgyvkYSWFLHVINFESISVEF 2050
Cdd:cd21686    81 vqqplqTTDYTvyalSLILYLANMTLFMGTFIVTFFVNFYGVGIPF-----------------YGWLLIDVPQSAFMMTF 143

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2051 VIIvIVFEAVLALKHIFFPCNNPSCKTCSKIARQTRIPIQVVVNGSMKTVYVHANGTGKLCKKHNFYCKNCDSYGFDHTF 2130
Cdd:cd21686   144 SVF-FFYYVLKFFVHVTHGCKIPTCMVCAKLARPPRVEVETVVQGRKYSFYVYTNGGFTFCKEHNFYCKNCDLYGPGCTF 222

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2131 ICDEIVRDLSNSVKQTVYATDKSYQEVTKVECSDgfyrfyvgeeftaYDYDVKHK-KYSSQEVLKTMFLLDDFIVYSPSG 2209
Cdd:cd21686   223 ISDEVAEELSRATKLSVKPTAPAFLLVDDVEVQN-------------DVVFARAKyNQNAHVSLSKFSDIPDFIIAANFG 289

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2210 S---SLASVRNVCVYFSQLIGRPIKIVNSDLLEDLSVDFkgalfnakKNVIKNSFNVDVSECKNLEEC---YKACNLDVT 2283
Cdd:cd21686   290 SnceQLSTAKNAAVYYSQDLCKPILILDQALSRPIDNYQ--------EVASRIEKYYPVAKIKPTGDIftdIKQGTDGEA 361

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2284 FSTFEMAINNAHRFGILITDRSFNNFWPSKIKPgSSGVSAMDIGkcMTFDAKIVNAKVLTQRGKSVVWLSQDFSALSSTA 2363
Cdd:cd21686   362 SDSAINAAVLAHQRDVEFTGDSFNNILPSYAKD-ESKLTAEDQA--MSVIAESGNANVNVKGTIPVVWLVADFIRLSEQA 438

                         490       500
                  ....*....|....*....|
gi 240015189 2364 QKVLVKTFVEEGVNFSLTFN 2383
Cdd:cd21686   439 RKYIISAAKKNGVTFALTPS 458

CoV_NSP10

pfam09401

Coronavirus RNA synthesis protein NSP10; Non-structural protein 10 (NSP10) is involved in RNA ...

3892-4010

6.61e-75

Pssm-ID: 462788 Cd Length: 119 Bit Score: 245.04 E-value: 6.61e-75

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  3892 GLLTLCAFAPDPAKAYVDAVKRGMQPVTNCVKMLSNGAGNGMAVTNGVESNTQQDSYGGASVCIYCRCHVEHPAIDGLCR 3971
Cdd:pfam09401    1 SLLSLCAFAVDPAKAYLDYLAQGGQPITNCVKMLCNHAGTGMAITVKPEANTDQDSYGGASVCLYCRAHIEHPNVDGLCQ 80

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 240015189  3972 FKGKFVQVPTGTQDPIRFCIENEICVVCGCWLNNGCMCD 4010
Cdd:pfam09401   81 LKGKFVQIPTGTKDPVSFCLTNTVCTVCGCWLGYGCSCD 119

TGEV-like_alphaCoV_Nsp1

cd21687

non-structural protein 1 from transmissible gastroenteritis virus and similar ...

2-105

2.72e-69

Pssm-ID: 439284 Cd Length: 104 Bit Score: 228.52 E-value: 2.72e-69

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189    2 SSKHFKILVNEDYQVNVPSLPFRDVSQEIKYCYRNGFDGYVFVPEYRRDLVDCNRKDHYVIGVLGNGISDLKPVLLTEPS 81
Cdd:cd21687     1 SSKQFKILVNEDYQVNVPSLPFRDVLQEIKYCYRNGFDGYVFVPEYRRDLVDCDRKDHYVIGVLGNGISDLKPVLLTEPS 80

                          90       100
                  ....*....|....*....|....
gi 240015189   82 VMLQGFIVRANCNGVLEDFDLKIA 105
Cdd:cd21687    81 VMLQGFIVRANCNGVLEDFDLKIA 104

CNV-Replicase_N

pfam16688

Replicase polyprotein N-term from Coronavirus nsp1; CNV-Replicase_N is the N-terminal domain ...

1-108

7.02e-68

Pssm-ID: 465234 Cd Length: 108 Bit Score: 224.87 E-value: 7.02e-68

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189     1 MSSKHFKILVNEDYQVNVPSLPFRDVSQEIKYCYRNGFDGYVFVPEYRRDLVDCNRKDHYVIGVLGNGISDLKPVLLTEP 80
Cdd:pfam16688    1 MSSKQFKILVNEDYQVNVPSLPFRDVLQDIKYCYRNGFDGYVFVPEYRRDLVDCNRKDHYVIGVLGNGISDLKPVLLTEP 80

                           90       100
                   ....*....|....*....|....*...
gi 240015189    81 SVMLQGFIVRANCNGVLEDFDLKIARTG 108
Cdd:pfam16688   81 SVMLQGFIVRADCNGVLEDFDLKIARTG 108

betaCoV_Nsp8

cd21831

betacoronavirus non-structural protein 8; This model represents the non-structural protein 8 ...

3578-3769

1.39e-67

betacoronavirus non-structural protein 8; This model represents the non-structural protein 8 (Nsp8) the highly pathogenic betacoronaviruses that include Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9, and Nsp10 form functional complexes with CoV core enzymes and thereby stimulate replication. Most importantly, a complex of Nsp8 with Nsp7 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the genes encoding Nsp8 and Nsp7 have been shown to delay virus growth. Nsp8 and Nsp7 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp8 with Nsp7 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp8 has a novel 'golf-club' fold composed of an N-terminal 'shaft' domain and a C-terminal 'head' domain. The shaft domain contains three helices, one of which is very long, while the head domain contains another three helices and seven beta-strands, forming an alpha/beta fold. SARS-CoV Nsp8 forms a 8:8 hexadecameric supercomplex with Nsp7 that adopts a hollow cylinder-like structure with a large central channel and positive electrostatic properties in the cylinder; the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to the template length.

Pssm-ID: 409258 Cd Length: 196 Bit Score: 227.36 E-value: 1.39e-67

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3578 SAYAALPSWIAYEKARADLEEAKKN-DVSPQLLKQLTKACNIAKSEFEREVSVQKKLDKMAEQAAASMYKEARAVDRKSK 3656
Cdd:cd21831     1 SEFSNLASYAEYETAQKAYDEAVASgDASPQVLKALKKAVNVAKSAYEKDKAVARKLERMADQAMTSMYKQARAEDKKSK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3657 IVSAMHSLLFGMLKKLDMSSVNTIIEQARNGVLPLSIIPAASATRLIVVTPNLEVLSKVRQENNVHYAGAIWSIVEVKDA 3736
Cdd:cd21831    81 VVSAMQTMLFGMIRKLDNDALNNIINNARNGCVPLSIIPLTAANKLRVVVPDYSVYKQVVDGPTLTYAGALWDIQQINDA 160

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 240015189 3737 NGSQVHLKEVTAANElNITWPLSITCER----TTKLQ 3769
Cdd:cd21831   161 DGKIVQLSDITEDSE-NLAWPLVVTATRanssAVKLQ 196

alphaCoV_Nsp9

cd21897

alphacoronavirus non-structural protein 9; This model represents the non-structural protein 9 ...

3770-3880

1.02e-64

Pssm-ID: 409330 Cd Length: 108 Bit Score: 215.64 E-value: 1.02e-64

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3770 NNEILPGKLKEKAVKASATIdgdAYGSGKALMASESGKSFIYAFVASDSNLKYVKWESNNDLIPIELEAPLRFYVDGVNG 3849
Cdd:cd21897     1 NNEIMPGKLKQRAVKAEGDG---FSGDGKALYNNEGGKTFMYAFIADKPDLKYVKWEFDGGCNTIELEPPCKFLVDTPNG 77

                          90       100       110
                  ....*....|....*....|....*....|.
gi 240015189 3850 PEVKYLYFVKNLNTLRRGAVLGYIGATVRLQ 3880
Cdd:cd21897    78 PQIKYLYFVKNLNTLRRGAVLGYIGATVRLQ 108

deltaCoV_Nsp5_Mpro

cd21668

deltacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily ...

2895-3190

4.08e-64

deltacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily contains the coronavirus (CoV) non-structural protein 5 (Nsp5) also called the Main protease (Mpro), or 3C-like protease (3CLpro), found in deltacoronaviruses. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Mpro/Nsp5 is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. These enzymes belong to the MEROPS peptidase C30 family, where the active site residues His and Cys form a catalytic dyad. The structures of Mpro/Nsp5 consist of three domains with the first two containing anti-parallel beta barrels and the third consisting of an arrangement of alpha-helices. The catalytic residues are found in a cleft between the first two domains. Mpro/Nsp5 requires a Gln residue in the P1 position of the substrate and space for only small amino-acid residues such as Gly, Ala, or Ser in the P1' position; since there is no known human protease with a specificity for Gln at the cleavage site of the substrate, these viral proteases are suitable targets for the development of antiviral drugs.

Pssm-ID: 394889 Cd Length: 302 Bit Score: 221.99 E-value: 4.08e-64

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2895 QSGLRKMAQPSGIVEPCIVRVAYGNNVLNGLWIGDEVICPRHVIASDTSRviNYENELSSVRLHNFSI--AKNNVFLGVV 2972
Cdd:cd21668     1 QAGIKILLHPSGVVERCMVSVTYNGSTLNGIWLHNVVYCPRHVIGKYTGS--QWQDMVSIADCRDFVIfcPTQGIQLTVQ 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2973 SVKYKGVNLVLKVNQVNPNTPEHKFKSVKPGESFNILACYEGCPGSVYGVNMRSQGTIKGSFIAGTCGSVGYVLENGTLY 3052
Cdd:cd21668    79 SVKMVGAVLQLTVHTKNLHTPDYEFERATPGSSMTIACAYDGIVRNVYHVVLQTNNLIYASFLNGACGSVGYTLKGKTLL 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3053 FVYMHHLELGNGSHVGSNLEGEMYGGYEDQPSMQLEGTNVMSSDNVVAFLYAALINGER---WFVTNAsMSLESYNAWAK 3129
Cdd:cd21668   159 LHYMHHLEFNNKTHGGTDLHGHFYGPYVDEEVAQHQTAFQYYTDNVVAQIYAHLLTIDAkpkWLASQE-ISVEDFNEWAA 237

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 240015189 3130 TNSFTEIVSTDAfNM-----LAAKTGYSVEKLLECIVRLNKGFGGRTILSYGSLCDEFTPTEVIRQ 3190
Cdd:cd21668   238 NNSFANFPCESS-NMaylegLAQTTKVSVGRVLNTIIQLTLNRGGALIMGKPDFECDWTPEMVYNQ 302

CoV_Nsp10

cd21872

coronavirus non-structural protein 10; This model represents the non-structural protein 10 ...

3881-4010

9.92e-55

coronavirus non-structural protein 10; This model represents the non-structural protein 10 (Nsp10) of alpha-, beta-, gamma- and deltacoronaviruses, including highly pathogenic betacoronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9, and Nsp10 form functional complexes with CoV core enzymes and thereby stimulate replication. Coronaviruses cap their mRNAs; RNA cap methylation may involve at least three proteins: Nsp10, Nsp14, and Nsp16. Nsp10 serves as a cofactor for both Nsp14 and Nsp16. Nsp14 consists of 2 domains with different enzymatic activities: an N-terminal ExoN domain and a C-terminal cap (guanine-N7) methyltransferase (N7-MTase) domain. The association of Nsp10 with Nsp14 enhances Nsp14's exoribonuclease (ExoN) activity, and not its N7-Mtase activity. ExoN is important for proofreading and therefore, the prevention of lethal mutations. The Nsp10/Nsp14 complex hydrolyzes double-stranded RNA in a 3' to 5' direction as well as a single mismatched nucleotide at the 3'-end, mimicking an erroneous replication product, and may function in a replicative mismatch repair mechanism. Nsp16 Cap-0 specific (nucleoside-2'-O-)-methyltransferase (2'OMTase) acts sequentially to Nsp14 MTase in RNA capping methylation, and methylates the RNA cap at the ribose 2'-O position; it catalyzes the conversion of the cap-0 structure on m7GpppA-RNA to a cap-1 structure. The association of Nsp10 with Nsp16 enhances Nsp16's 2'OMTase activity, possibly through enhanced RNA binding affinity. Additionally, transmissible gastroenteritis virus (TGEV) Nsp10, Nsp16, and their complex can interact with DII4, which normally binds to Notch receptors; this interaction may disturb Notch signaling. Nsp10 also binds 2 zinc ions with high affinity.

Pssm-ID: 409325 Cd Length: 131 Bit Score: 188.06 E-value: 9.92e-55

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3881 AGKPTEHPSNSGLLTLCAFAPDPAKAYVDAVKRGMQPVTNCVKMLSNGAGNGMAVTNGVESNTQQDSYGGASVCIYCRCH 3960
Cdd:cd21872     1 AGNATEVPANSTVLSFCAFAVDPAKAYKDYLASGGQPITNCVKMLCTHTGTGQAITVKPEANMDQESFGGASVCLYCRAH 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 240015189 3961 VEHPAIDGLCRFKGKFVQVPTGTQ-DPIRFCIENEICVVCGCWLNNGCMCD 4010
Cdd:cd21872    81 IDHPNPDGFCDYKGKFVQIPTTCAnDPVGFTLRNTVCTVCQMWKGYGCSCD 131

TM_Y_betaCoV_Nsp3_C

cd21713

C-terminus of betacoronavirus non-structural protein 3, including transmembrane and Y domains; ...

1913-2383

1.32e-54

C-terminus of betacoronavirus non-structural protein 3, including transmembrane and Y domains; This model represents the C-terminus of non-structural protein 3 (Nsp3) from betacoronavirus, including highly pathogenic betacoronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. This conserved C-terminus includes two transmembrane (TM) regions TM1 and TM2, an ectodomain (3Ecto) between the TM1 and TM2 that is glycosylated and located on the lumenal side of the ER, an amphiphatic region (AH1) that is not membrane-spanning, and a large Y domain of approximately 370 residues. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. In SARS-CoV and murine hepatitis virus (MHV), the TM1, 3Ecto and TM2 domains are important for the papain-like protease (PL2pro) domain to process Nsp3-Nsp4 cleavage. It has also been shown that the interaction of 3Ecto with the lumenal loop of Nsp4 is essential for ER rearrangements in cells infected with SARS-CoV or MHV. The Y domain, located at the cytosolic side of the ER, consists of the Y1 and CoV-Y subdomains, which are conserved in nidovirus and coronavirus, respectively. Functional information about the Y domain is limited; it has been shown that Nsp3 binding to Nsp4 is less efficient without the Y domain.

Pssm-ID: 409661 Cd Length: 545 Bit Score: 202.34 E-value: 1.32e-54

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1913 LVLLLIALYHFFYLFVSIPLVHKL-----ACSGSVQAYSNSS----FVKSEVCGNSILCKACLASYDELADFDHLQVSWD 1983
Cdd:cd21713    12 LLLWFNFLYANFILSDSPTFVGSIvawfkYTLGISTICDFYQvtylGDISEFCTGSMLCSLCLSGMDSLDNYDALNMVQH 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1984 YKSDPLWNrvmqLSYFTFLAVFGNNYVRFCLMYFVT------QYLNLWLSYFgYVKYSW----FLHVINFESIS--VEFV 2051
Cdd:cd21713    92 TVSSRLSD----DYIFKLVLELFFAYLLYTVAFYVLgllailQLFFSYLPLF-FMLNSWlvvlFVYVINMVPAStlVRMY 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2052 IIVIVFEAVL-ALKHIFFPCNNPSCKTCSKIARQTRIPIQVVVNGSMKTVYVHANGTGKLCKKHNFYCKNCDSYGFDHTF 2130
Cdd:cd21713   167 IVVASLYFVYkLYVHVVYGCNDTACLMCYKRNRATRVECSTVVNGSKRSFYVMANGGTGFCTKHNWNCVNCDTYGPGNTF 246

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2131 ICDEIVRDLSNSVKQTVYATDKSYQEVTKVECSDGFYRFY-------VGEEFTA-YDYDVKHKKYSSqevLKTMFLLDDF 2202
Cdd:cd21713   247 ICDEVAADLSTQFKRPINPTDSSYYSVTSVEVKNGSVHLYyerdgqrVYERFSLsLFVNLDKLKHSE---VKGSPPFNVI 323

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2203 IVYSPSGSSLASVRNVCVYFSQLIGRPIKIVNSDLLEDL--SVDFKGALFNAKKNVIKNSFNVDVSECKNL-----EECY 2275
Cdd:cd21713   324 VFDASNRAEENGAKSAAVYYSQLLCKPILLVDKKLVTTVgdSAEVARKMFDAYVNSFLSTYNVTMDKLKTLvstahNSLK 403

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2276 KACNLDVTFSTF-------------------EMAINNAHRFGILITDRSFNNFWPSKIKPGSsgVSAMDIGKCMTFDAKI 2336
Cdd:cd21713   404 EGVQLEQVLKTFigaarqkaavesdvetkdiVKCVQLAHQADVDFTTDSCNNLVPTYVKVDT--ITTADLGVLIDNNAKH 481

                         490       500       510       520
                  ....*....|....*....|....*....|....*....|....*..
gi 240015189 2337 VNAKVLTQRGKSVVWLSQDFSALSSTAQKVLVKTFVEEGVNFSLTFN 2383
Cdd:cd21713   482 VNANVAKAANVALIWNVAAFLKLSESLRRQLRSAARKTGLNFKLTTS 528

CoV_NSP9

pfam08710

Coronavirus replicase NSP9; Nsp9 is a single-stranded RNA-binding viral protein involved in ...

3770-3880

2.60e-52

Pssm-ID: 285872 Cd Length: 111 Bit Score: 180.37 E-value: 2.60e-52

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  3770 NNEILPGKLKEKAVKASATiDGDAYGSGKALMASESGKSFIYAFVASDSNLKYVKWESNND-LIPIELEAPLRFYVDGVN 3848
Cdd:pfam08710    1 NNELMPGKLKTKACKAGVT-DAHCSVEGKAYYNNEGGGSFVYAILSSNPNLKYAKFEKEDGnVIYVELEPPCRFVVDTPK 79

                           90       100       110
                   ....*....|....*....|....*....|..
gi 240015189  3849 GPEVKYLYFVKNLNTLRRGAVLGYIGATVRLQ 3880
Cdd:pfam08710   80 GPEVKYLYFVKNLNNLRRGMVLGYISATVRLQ 111

gammaCoV_Nsp8

cd21832

gammacoronavirus non-structural protein 8; This model represents the non-structural protein 8 ...

3575-3766

2.09e-51

gammacoronavirus non-structural protein 8; This model represents the non-structural protein 8 (Nsp8) region of gammacoronaviruses that include Avian infectious bronchitis virus (IBV) and Canada goose coronavirus (CGCoV), among others. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9, and Nsp10 form functional complexes with CoV core enzymes and thereby stimulate replication. Most importantly, a complex of Nsp8 with Nsp7 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the genes encoding Nsp8 and Nsp7 have been shown to delay virus growth. Nsp8 and Nsp7 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp8 with Nsp7 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp8 has a novel 'golf-club' fold composed of an N-terminal 'shaft' domain and a C-terminal 'head' domain. The shaft domain contains three helices, one of which is very long, while the head domain contains another three helices and seven beta-strands, forming an alpha/beta fold. SARS-CoV Nsp8 forms a 8:8 hexadecameric supercomplex with Nsp7 that adopts a hollow cylinder-like structure with a large central channel and positive electrostatic properties in the cylinder, while Feline infectious peritonitis virus Nsp8 forms a 1:2 heterotrimer with Nsp7. Regardless of their oligomeric structure, the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to the template length.

Pssm-ID: 409259 Cd Length: 210 Bit Score: 181.69 E-value: 2.09e-51

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3575 SVASAYAALPSWIAYEKARADLEE----AKKNDVSPQLLKQLTKACNIAKSEFEREVSVQKKLDKMAEQAAASMYKEARA 3650
Cdd:cd21832     1 SVTQEFSHIPSYAEYERAKDLYEKvladSKNGGVTQQELAAYRKAANIAKSVFDRDLAVQKKLDSMAERAMTTMYKEARV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3651 VDRKSKIVSAMHSLLFGMLKKLDMSSVNTIIEQARNGVLPLSIIPAASATRLIVVTPNLEVLSKVRQENNVHYAGAIWSI 3730
Cdd:cd21832    81 TDRRAKLVSSLHALLFSMLKKIDSEKLNVLFDQASSGVVPLATVPIVCSNKLTLVIPDPETWVKCVEGMHVTYSTVVWNI 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 240015189 3731 VEVKDANGSQVHlkEVTAANEL-------NITWPLSITCERTT 3766
Cdd:cd21832   161 DTVIDADGTELH--PTSTGSGLtycisgdNIAWPLKVNLTRNG 201

CoV_NSP4_C

pfam16348

Coronavirus replicase NSP4, C-terminal; This is the C-terminal domain of the coronavirus ...

2803-2894

1.97e-49

Pssm-ID: 465099 Cd Length: 92 Bit Score: 171.17 E-value: 1.97e-49

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  2803 GDKFVGSFESAAMGTFVIDMRSYETLVNSTSLDRIKSYANSFNKYKYYTGSMGEADYRMACYAHLGKALMDYSVSRNDML 2882
Cdd:pfam16348    1 GDKFVGTFEEAALGTFVIDKESYEKLKNSISLDKFNRYLSLYNKYKYYSGKMDEADYREACCAHLAKALEDFSNSGNDVL 80

                           90
                   ....*....|..
gi 240015189  2883 YTPPTVSVNSTL 2894
Cdd:pfam16348   81 YTPPTVSVTSSL 92

Macro_X_Nsp3-like

cd21557

X-domain (or Mac1 domain) of viral non-structural protein 3 and related macrodomains; The ...

1355-1482

6.99e-48

Pssm-ID: 438957 Cd Length: 127 Bit Score: 168.12 E-value: 6.99e-48

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1355 PDVVVNAANGDLRHLGGVAKAIDNFTGGKLTKRSkDYLKSNKSIAPGNAVLFENVLEHLSVLNAVGPRNGDSRVEGKLCN 1434
Cdd:cd21557     1 EDVVVNAANENLKHGGGVAGAIYKATGGAFQKES-DYIKKNGPLKVGTAVLLPGHGLAKNIIHVVGPRKRKGQDDQLLAA 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 240015189 1435 VYKAIAKCDGKILTPLISVGIFNVKLEVSLQCLLKTVTDRDLNVFVYT 1482
Cdd:cd21557    80 AYKAVNKEYGSVLTPLLSAGIFGVPPEQSLNALLDAVDTTDADVTVYC 127

alphaCoV_Nsp7

cd21826

alphacoronavirus non-structural protein 7; This model represents the non-structural protein 7 ...

3492-3574

3.73e-47

Pssm-ID: 409252 Cd Length: 83 Bit Score: 164.46 E-value: 3.73e-47

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3492 SKLTEMKCTNVVLLGLLSKMHVESNSKEWNYCVGLHNEINLCDDPEVVLEKLLALIAFFLSKHNTCDLSDLIDSYFENTT 3571
Cdd:cd21826     1 SKLTDIKCTNVVLLGCLSSMNVAANSKEWAYCVDLHNKINLCDDPEKAQEMLLALLAFFLSKQKDFGLDDLLDSYFDNNS 80


                  ...
gi 240015189 3572 ILQ 3574
Cdd:cd21826    81 ILQ 83

gammaCoV_Nsp10

cd21902

gammacoronavirus non-structural protein 10; This model represents the non-structural protein ...

3882-4010

8.41e-47

gammacoronavirus non-structural protein 10; This model represents the non-structural protein 10 (Nsp10) of gammacoronaviruses, including Infectious bronchitis virus (IBV)and Bottlenose dolphin coronavirus HKU22(BdCoV HKU22). CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9, and Nsp10 form functional complexes with CoV core enzymes and thereby stimulate replication. Coronaviruses cap their mRNAs; RNA cap methylation may involve at least three proteins: Nsp10, Nsp14, and Nsp16. Nsp10 serves as a cofactor for both Nsp14 and Nsp16. Nsp14 consists of 2 domains with different enzymatic activities: an N-terminal ExoN domain and a C-terminal cap (guanine-N7) methyltransferase (N7-MTase) domain. The association of Nsp10 with Nsp14 enhances Nsp14's exoribonuclease (ExoN) activity, and not its N7-Mtase activity. ExoN is important for proofreading and therefore, the prevention of lethal mutations. The Nsp10/Nsp14 complex hydrolyzes double-stranded RNA in a 3' to 5' direction as well as a single mismatched nucleotide at the 3'-end, mimicking an erroneous replication product, and may function in a replicative mismatch repair mechanism. Nsp16 Cap-0 specific (nucleoside-2'-O-)-methyltransferase (2'OMTase) acts sequentially to Nsp14 MTase in RNA capping methylation and methylates the RNA cap at the ribose 2'-O position; it catalyzes the conversion of the cap-0 structure on m7GpppA-RNA to a cap-1 structure. The association of Nsp10 with Nsp16 enhances Nsp16's 2'OMTase activity, possibly through enhanced RNA binding affinity. Additionally, transmissible gastroenteritis virus (TGEV) Nsp10, Nsp16 and their complex can interact with DII4, which normally binds to Notch receptors; this interaction may disturb Notch signaling. Nsp10 also binds 2 zinc ions with high affinity.

Pssm-ID: 409327 Cd Length: 134 Bit Score: 165.45 E-value: 8.41e-47

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3882 GKPTEHPSNSGLLTLCAFAPDPAKAYVDAVKRGMQPVTNCVKMLSNGAGNGMAVTNGVESNTQQDSYGGASVCIYCRCHV 3961
Cdd:cd21902     2 GHETEEVDAVGILSLCSFAVDPADTYCKYVAAGNQPLGNCVKMLTVHNGSGFAITSKPSPTPDQDSYGGASVCLYCRAHI 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 240015189 3962 EHPA----IDGLCRFKGKFVQVPTGTQDPIRFCIENEICVVCGCWLNNGCMCD 4010
Cdd:cd21902    82 AHPGgagnLDGRCQFKGSFVQIPTTEKDPVGFCLRNKVCTVCQCWIGYGCQCD 134

CoV_Nsp6

cd21526

coronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host cell ...

3187-3491

2.02e-45

coronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host cell membranes as part of the viral genome replication and transcription machinery; they induce the formation of double-membrane vesicles in infected cells. CoV non-structural protein 6 (Nsp6), a transmembrane-containing protein, together with Nsp3 and Nsp4, have the ability to induce double-membrane vesicles that are similar to those observed in severe acute respiratory syndrome (SARS) coronavirus-infected cells. By itself, Nsp6 can generate autophagosomes from the endoplasmic reticulum. Autophagosomes are normally generated as a cellular response to starvation to carry cellular organelles and long-lived proteins to lysosomes for degradation. Degradation through autophagy may provide an innate defense against virus infection, or conversely, autophagosomes can promote infection by facilitating the assembly of replicase proteins. In addition to initiating autophagosome formation, Nsp6 also limits autophagosome expansion regardless of how they were induced, i.e. whether they were induced directly by Nsp6, or indirectly by starvation or chemical inhibition of MTOR signaling. This may favor coronavirus infection by compromising the ability of autophagosomes to deliver viral components to lysosomes for degradation.

Pssm-ID: 394843 Cd Length: 287 Bit Score: 167.32 E-value: 2.02e-45

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3187 VIRQMYGVNLQS---GKVKSLFYP--VMTAIAILFAFWLEFFMYtpftwinpAFVSVILAITtlvsaVLVVGIKHKMLFF 3261
Cdd:cd21526     1 VYNQAPGVLLQSvfvVKKTSTFWShfLFAAFTMLLAAPLVFPVH--------AYVILLMCFT-----VVTFTVKHKVAFL 67

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3262 MSFVMPSVILATA-HNVVWD------MTYYESlqalvenVNTTFLPVDMQGVMLALFCVVVFVTYTIRFFTCKQSWFSLF 3334
Cdd:cd21526    68 TTFLLPSLITMVAiANTFWIqvvtflRTWYDT-------VFVSPIAQDLYGYTVALYMLIYAGLATNYTLKTLRYRATSF 140

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3335 VTTVFVMFNI--VKLLGMIGEPWTddhillclVNMLTMLISLTTKDWFVVFVSYKVAYYIVvYVMHPAFvqdFGFIKCVS 3412
Cdd:cd21526   141 LSFLMQNFLTlyTAHYAYKLLPWT--------ESLLFTALTMLSSHSLIGAIVFWLARWML-RVEYPII---FPDLAIRV 208

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 240015189 3413 IIYMACGYLFCCYYGILYWVNRFTCMTCGVYQFTVSPAELKYMTANNLSAPKTAYDAMILSVKLMGIGGERNIKISTVQ 3491
Cdd:cd21526   209 LAYNVIGYVCTCYFGLMWLANRFFTLTLGVYDYMVSVEQFRYMMAVKLNPPKNAFEVFILNIKLLGIGGNRNIKVATVQ 287

CoV_NSP7

pfam08716

Coronavirus replicase NSP7; NSP7 (non structural protein 7) has been implicated in viral RNA ...

3492-3574

7.06e-43

Pssm-ID: 285878 Cd Length: 83 Bit Score: 152.22 E-value: 7.06e-43

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  3492 SKLTEMKCTNVVLLGLLSKMHVESNSKEWNYCVGLHNEINLCDDPEVVLEKLLALIAFFLSKHNTCDLSDLIDSYFENTT 3571
Cdd:pfam08716    1 SKLTDVKCTNVVLLGLLQKLHVESNSKLWAYCVELHNEILLCDDPTEAFEKLLALLAVLLSKHSAVDLSDLCDSYLENRT 80


                   ...
gi 240015189  3572 ILQ 3574
Cdd:pfam08716   81 ILQ 83

CoV_NSP2_C

Coronavirus replicase NSP2, C-terminal; This entry corresponds to a presumed domain found at ...

425-582

1.20e-42

Pssm-ID: 465996 Cd Length: 156 Bit Score: 154.34 E-value: 1.20e-42

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189   425 LCTSAFTIMDYKPVFVVShSSVKNLVDKCVKILVKAFDVFTQTITIAGVEAKCfvlGSKYLLFNNALVKLVSVKILGKRQ 504
Cdd:pfam19212    1 LKNAKFTVVNGGIVFVVP-KKFKSLVGTLLDLLNKLFDSLVDTVKIAGVKFKA---GGTYYLFSNALVKVVSVKLKGKKQ 76

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 240015189   505 KGLDSAFFVTNLIGATVNVTPQRTEAANISLNKVDDVV-TPGEGHIVIVGGMAFYKSEEYYFmMASPDSVLVNNVFKAA 582
Cdd:pfam19212   77 AGLKGAKEATVFVGATVPVTPTRVEVVTVELEEVDYVPpPVVVGYVVVIDGYAFYKSGDEYY-PASTDGVVVPPVFKLK 154

TM_Y_SARS-CoV-like_Nsp3_C

cd21717

C-terminus of non-structural protein 3, including transmembrane and Y domains, from Severe ...

1938-2381

8.21e-41

C-terminus of non-structural protein 3, including transmembrane and Y domains, from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage; This model represents the C-terminus of non-structural protein 3 (Nsp3) from betacoronavirus in the sarbecovirus subgenus (B lineage), including highly pathogenic human coronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV). This conserved C-terminus includes two transmembrane (TM) regions TM1 and TM2, an ectodomain (3Ecto) between the TM1 and TM2 that is glycosylated and located on the lumenal side of the ER, an amphiphatic region (AH1) that is not membrane-spanning, and a large Y domain of approximately 370 residues. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. In SARS-CoV and the related murine hepatitis virus (MHV), the TM1, 3Ecto and TM2 domains are important for the papain-like protease (PL2pro) domain to process Nsp3-Nsp4 cleavage. It has also been shown that the interaction of 3Ecto with the lumenal loop of Nsp4 is essential for ER rearrangements in cells infected with SARS-CoV or MHV. The Y domain, located at the cytosolic side of the ER, consists of the Y1 and CoV-Y subdomains, which are conserved in nidovirus and coronavirus, respectively. Functional information about the Y domain is limited; it has been shown that Nsp3 binding to Nsp4 is less efficient without the Y domain.

Pssm-ID: 409665 Cd Length: 531 Bit Score: 160.92 E-value: 8.21e-41

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1938 CSGSVQAYSNSSFVK-SEVCGNSILCKACLASYDELADFDHL---QVSWD-YKSDplwnrvmqLSYFTFLAVFGNNYVRF 2012
Cdd:cd21717    32 CDGVRESYLNSSNVTtMDFCEGSFPCSVCLSGLDSLDSYPALetiQVTISsYKLD--------LTILGLAAEWFLAYMLF 103

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2013 CLMYFV---TQYLNLWLSYFG--YVKYSWFL----HVINFESIS--VEFVIIVIVFEAVL-ALKHIFFPCNNPSCKTCSK 2080
Cdd:cd21717   104 TKFFYLlglSAIMQVFFGYFAshFISNSWLMwfiiSIVQMAPVSamVRMYIFFASFYYIWkSYVHIMDGCTSSTCMMCYK 183

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2081 IARQTRIPIQVVVNGSMKTVYVHANGTGKLCKKHNFYCKNCDSYGFDHTFICDEIVRDLSNSVKQTVYATDKSYQEVTKV 2160
Cdd:cd21717   184 RNRATRVECTTIVNGMKRSFYVYANGGRGFCKTHNWNCLNCDTFCAGSTFISDEVARDLSLQFKRPINPTDQSSYVVDSV 263

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2161 ECSDGFYRFYvgeeftaydYDVKHKKYSSQEVLKTMFLLDDF-------------IVYS-PSGSSLASVRNVCVYFSQLI 2226
Cdd:cd21717   264 AVKNGALHLY---------FDKAGQKTYERHPLSHFVNLDNLranntkgslpinvIVFDgKSKCDESAAKSASVYYSQLM 334

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2227 GRPIKIVNSDLLEDL--SVDFKGALFNAKKNVIKNSFNVDVSECKNL-----EECYKACNLDVTFSTFEMAINN------ 2293
Cdd:cd21717   335 CQPILLLDQALVSDVgdSTEVSVKMFDAYVDTFSATFSVPMEKLKALvatahSELAKGVALDGVLSTFVSAARQgvvdtd 414

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2294 ------------AHRFGILITDRSFNNFWPSKIKpgSSGVSAMDIGKCMTFDAKIVNAKVLTQRGKSVVWLSQDFSALSS 2361
Cdd:cd21717   415 vdtkdvieclklSHHSDLEVTGDSCNNFMLTYNK--VENMTPRDLGACIDCNARHINAQVAKSHNVSLIWNVKDYMSLSE 492

                         490       500
                  ....*....|....*....|
gi 240015189 2362 TAQKVLVKTFVEEGVNFSLT 2381
Cdd:cd21717   493 QLRKQIRSAAKKNNIPFRLT 512

TM_Y_MERS-CoV-like_Nsp3_C

cd21716

C-terminus of non-structural protein 3, including transmembrane and Y domains, from Middle ...

1937-2397

2.03e-40

C-terminus of non-structural protein 3, including transmembrane and Y domains, from Middle East respiratory syndrome-related coronavirus and betacoronavirus in the C lineage; This model represents the C-terminus of non-structural protein 3 (Nsp3) from betacoronavirus in the merbecovirus subgenus (C lineage), including Middle East respiratory syndrome-related coronavirus (MERS-CoV) and Tylonycteris bat coronavirus HKU4. This conserved C-terminus includes two transmembrane (TM) regions TM1 and TM2, an ectodomain (3Ecto) between the TM1 and TM2 that is glycosylated and located on the lumenal side of the ER, an amphiphatic region (AH1) that is not membrane-spanning, and a large Y domain of approximately 370 residues. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. In the related betacoronaviruses, Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and murine hepatitis virus (MHV), the TM1, 3Ecto and TM2 domains are important for the papain-like protease (PL2pro) domain to process Nsp3-Nsp4 cleavage. It has also been shown that the interaction of 3Ecto with the lumenal loop of Nsp4 is essential for ER rearrangements in cells infected with SARS-CoV or MHV. The Y domain, located at the cytosolic side of the ER, consists of the Y1 and CoV-Y subdomains, which are conserved in nidovirus and coronavirus, respectively. Functional information about the Y domain is limited; it has been shown that Nsp3 binding to Nsp4 is less efficient without the Y domain.

Pssm-ID: 409664 Cd Length: 566 Bit Score: 160.36 E-value: 2.03e-40

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1937 ACSGSVQAYSNSSFVKSEVCGN-SILCKACLASYDELADFDHLQVSWDYKS------DPLWNRV-MQLSYFTFLAVFGNN 2008
Cdd:cd21716    55 ACDGLASAYRANSFDVPDFCANrSALCNWCLIGQDSITHYSALKMVQTHLShyvlniDWLWFALeLLLAYVLYTSAFNWL 134

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2009 YVRFCLMYFVTQ---YLNlWLSYfGYVKYSWFLHvinFESISVEFVIIVIVFEAVLAL-----KHIFFPCNNPSCKTCSK 2080
Cdd:cd21716   135 LLACTLQYFFAQtsaFVD-WRSY-NYVVSGIFLL---FTHIPLDGLVRIYNVLACLWFlrkfyNHVINGCKDTACLLCYK 209

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2081 IARQTRIPIQVVVNGSMKTVYVHANGTGKLCKKHNFYCKNCDSYGFDHTFICDEIVRDLSNSVKQTVYATDKSYQEVTKV 2160
Cdd:cd21716   210 RNRLTRVEASTVVCGGKRTFYITANGGTSFCRRHNWNCVDCDTAGVGNTFICEEVANDLTTSLRRLVKPTDRSHYYVDSV 289

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2161 ECSDGFYRF-YVGEEFTAYD-----YDVKHKKYSSQEVLKTMFLLDD--FIVYSPSG---SSLAsvRNVCVYFSQLIGRP 2229
Cdd:cd21716   290 EVKDTVVQLnYRRDGQSCYErfplcYFTNLDKLKFKEVCKTTTGIPEhnFIIYDSSDrgqENLA--RSACVYYSQVLCKP 367

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2230 IKIVNSDLLEDL--SVDFKGALFNAKKNVIKNSFNVDVSECKNLEECYKAC-----NLDVTFSTFEMA------------ 2290
Cdd:cd21716   368 ILLVDSNLVTSVgdSSEIAIKMFDSFVNSFVSLYNVTRDKLEKLISTARDGvkrgdNFQSVLKTFIDAargpagvesdve 447

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2291 -------INNAHRFGILITDRSFNNFWPSKIKPGSsgVSAMDIGKCMTFDAKIVNAKVLTQRGKSVVWLSQDFSALSSTA 2363
Cdd:cd21716   448 tneivdaVQYAHKHDIQLTTESYNNYVPSYVKPDS--VATSDLGSLIDCNAASVNQTSMRNANGACIWNAAAYMKLSDSL 525

                         490       500       510
                  ....*....|....*....|....*....|....
gi 240015189 2364 QKVLVKTFVEEGVNFSLTFNAVGSDEDLPYERFT 2397
Cdd:cd21716   526 KRQIRIACRKCNLNFRLTTSKLRANDNILSVKFS 559

betaCoV-Nsp6

cd21560

betacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host cell ...

3199-3491

2.39e-39

betacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host cell membranes as part of the viral genome replication and transcription machinery; they induce the formation of double-membrane vesicles in infected cells. CoV non-structural protein 6 (Nsp6), a transmembrane-containing protein, together with Nsp3 and Nsp4, have the ability to induce double-membrane vesicles that are similar to those observed in severe acute respiratory syndrome (SARS) coronavirus-infected cells. By itself, Nsp6 can generate autophagosomes from the endoplasmic reticulum. Autophagosomes are normally generated as a cellular response to starvation to carry cellular organelles and long-lived proteins to lysosomes for degradation. Degradation through autophagy may provide an innate defense against virus infection, or conversely, autophagosomes can promote infection by facilitating the assembly of replicase proteins. In addition to initiating autophagosome formation, Nsp6 also limits autophagosome expansion regardless of how they were induced, i.e. whether they were induced directly by Nsp6, or indirectly by starvation or chemical inhibition of MTOR signaling. This may favor coronavirus infection by compromising the ability of autophagosomes to deliver viral components to lysosomes for degradation.

Pssm-ID: 394846 Cd Length: 290 Bit Score: 150.08 E-value: 2.39e-39

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3199 GKVKSLFYPVMTAIAILFA----FWLEFFMYTPFTWINPAFVSVILAITTLVSAVLVVGIKHKMLFFMSFVMPSVILATA 3274
Cdd:cd21560     1 SKVKRVVKGTLHWLLATFVlfylIILQLTKWTMFMYLTETMLLPLTPALCCVSACVMLLVKHKHTFLTLFLLPVLLTLAY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3275 HNVVWdmTYYESLQALVENVNTTFLP-VDMQGVMLALFCVVVFVTYTIRFFTCKQSWFSLfvttVFVMFNIVKLLGMIGE 3353
Cdd:cd21560    81 YNYVY--VPKSSFLGYVYNWLNYVNPyVDYTYTDEVTYGSLLLVLMLVTMRLVNHDAFSR----VWAVCRVITWVYMWYT 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3354 PWTDDHILLclvnMLTMLISLTTKDWFVVFVSYKVAYYIVVYVMH--PAFVQDFGFIKCVSIIYMACGYLFCCYYGILYW 3431
Cdd:cd21560   155 GSLEESALS----YLTFLFSVTTNYTGVVTVSLALAKFITALWLAynPLLFLDIPEVKCVLLVYLFIGYICTCYFGVFSL 230

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3432 VNRFTCMTCGVYQFTVSPAELKYMTANNLSAPKTAYDAMILSVKLMGIGGERNIKISTVQ 3491
Cdd:cd21560   231 LNRLFRCPLGVYDYKVSTQEFRYMNANGLRPPRNSWEALMLNFKLLGIGGVPCIKVSTVQ 290

CoV_peptidase

Coronavirus papain-like peptidase; This entry contains coronavirus cysteine endopeptidases ...

1496-1793

5.66e-39

Pssm-ID: 430171 Cd Length: 318 Bit Score: 149.75 E-value: 5.66e-39

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  1496 TIPVKVTEDTVNQKRVSVALDKTYGEQLkGTVVIKDKDVTNQLPSVSDAGEKVVKALDVDWNAYYGFPNAAAFSASSHDA 1575
Cdd:pfam08715    4 QITIYLTEDGVNYHSIVVKPGDSLGQQF-GQVYAKNKDLSGVFPADDVEDKEILYVPTTDWVEFYGFKSILEYYTLDASK 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  1576 Y-------KFDVVTHNNFIVHKQTDNNCWVNAICLALQRLKPTWKFPGVKSLWDVFLTRKTAGFVHMLYHISGLKKGQPG 1648
Cdd:pfam08715   83 YviylsalTKNVQYVDGFLILKWRDNNCWISSVIVALQAAKIRFKGQFLTEAWAKLLGGDPTDFVAWCYASCTAKVGDFG 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  1649 DAELTLHKLGELMVSDSIVTITHTTACDKCAKIENFTGPVVAAPLMI--------YGTDETCVHGVSVNVKVTSIRGTVA 1720
Cdd:pfam08715  163 DANWTLTNLAEHFDAEYTNAFLKKRVCCNCGIKSYELRGLEACIQVRatnldhfkTGYSNCCVCGANNTDEVIEASLPYL 242

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 240015189  1721 ITSLIG--PVVGDVIDATGYICYTGLNSRGHYtYYDNRNGLMVDAEKAYHFEKNLLQVTtaiaSNFVSNTPKNET 1793
Cdd:pfam08715  243 LLSATDgpAAVDCLEDGVGTVAFVGSTNSGHY-TYQTAKQAFYDGAKDRKFGKKSPYVT----AVYTRFAFKNET 312

alpha_betaCoV_Nsp1

cd21874

non-structural protein 1 from alpha- and betacoronavirus; This model represents the ...

3-104

2.68e-38

non-structural protein 1 from alpha- and betacoronavirus; This model represents the non-structural protein 1 (Nsp1) from alpha- and betacoronaviruses, including highly pathogenic betacoronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. Gamma- and deltaCoVs do not have Nsp1. CoVs utilize a multi-subunit replication/transcription machinery assembled from a set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins. Nsp1 is the N-terminal cleavage product released from the ORF1a polyprotein by the action of papain-like protease (PLpro). Though Nsp1s of alphaCoVs and betaCoVs share structural similarity, they show no significant sequence similarity and may be considered as genus-specific markers. Despite low sequence similarity, the Nsp1s of alphaCoVs and betaCoVs exhibit remarkably similar biological functions, and are involved in the regulation of both host and viral gene expression. CoV Nsp1 induces suppression of host gene expression and interferes with host immune response. It inhibits host gene expression in two ways: by targeting the translation and stability of cellular mRNAs, and by inhibiting mRNA translation and inducing an endonucleolytic RNA cleavage in the 5'-UTR of cellular mRNAs through its tight association with the 40S ribosomal subunit, a key component of the cellular translation machinery. Inhibition of host mRNA translation includes that of type I interferons, major components of the host innate immune response. Nsp1 is critical in regulating viral replication and gene expression, as shown by multiple evidences, including: mutations in the Nsp1 coding region of the transmissible gastroenteritis virus (TGEV) and murine hepatitis virus (MHV) genomes cause drastic reduction or elimination of infectious virus; bovine coronavirus (BCoV) Nsp1 is an RNA-binding protein that interacts with cis-acting replication elements in the 5'-UTR of the BCoV genome, implying its potential role in the regulation of viral translation or replication; and SARS-CoV Nsp1 enhances virus replication by binding to a stem-loop structure in the 5'-UTR of its genome.

Pssm-ID: 409336 Cd Length: 103 Bit Score: 140.04 E-value: 2.68e-38

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189    3 SKHFKILVNE-DYQVNVPSLPFRDVSQEIKYCYRNGFDGYVFVPEYRRDLVDCNRKDHYVIGVLGNGISDLKPVLLTEPS 81
Cdd:cd21874     1 SVQLSLPVLQvDVLVRGFGDSVEEALSEAREHLKNGFGTCGFVELEKGDLVDCPQLEQYVVFVKGSKVVELVAEMDGIRS 80

                          90       100
                  ....*....|....*....|...
gi 240015189   82 VMLQGFIVRANCNGVLEDFDLKI 104
Cdd:cd21874    81 GITLGVLVPHNCNIALENVLLRK 103

CoV_Nsp7

cd21811

coronavirus non-structural protein 7; This model represents the non-structural protein 7 (Nsp7) ...

3492-3574

7.39e-38

coronavirus non-structural protein 7; This model represents the non-structural protein 7 (Nsp7) of alpha-, beta-, gamma- and deltacoronaviruses, including highly pathogenic betacoronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9 and Nsp10 form functional complexes with CoV core enzymes and stimulate replication. Most importantly, a complex of Nsp7 with Nsp8 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the NSP7- or NSP8-coding region have been shown to delay virus growth. Nsp7 and Nsp8 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp7 with Nsp8 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp7 has a 4-helical bundle conformation which is strongly affected by its interaction with Nsp8, especially where it concerns alpha-helix 4. SARS-CoV Nsp7 forms a 8:8 hexadecameric supercomplex with Nsp8 that adopts a hollow cylinder-like structure with a large central channel and positive electrostatic properties in the cylinder, while Feline infectious peritonitis virus Nsp7 forms a 2:1 heterotrimer with Nsp8. Regardless of their oligomeric structure, the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to template length.

Pssm-ID: 409251 Cd Length: 83 Bit Score: 138.00 E-value: 7.39e-38

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3492 SKLTEMKCTNVVLLGLLSKMHVESNSKEWNYCVGLHNEINLCDDPEVVLEKLLALIAFFLSKHNTCDLSDLIDSYFENTT 3571
Cdd:cd21811     1 SKLTDVKCTAVVLLSLLQKLRVESNSKLWKQCVQLHNDILLAKDTTEVFEKLVSLLSVLLSMQGAVDLNRLCEEMLENRA 80


                  ...
gi 240015189 3572 ILQ 3574
Cdd:cd21811    81 VLQ 83

CoV_PLPro

cd21688

Coronavirus (CoV) papain-like protease (PLPro); This model represents the papain-like protease ...

1496-1765

1.79e-36

Pssm-ID: 409647 Cd Length: 299 Bit Score: 141.85 E-value: 1.79e-36

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1496 TIPVKVTEDTVNQKRVSVALDKTYGEQLkGTVVIKDKDVTNQLPSVSDAGEKVV--KALDVDWNAYYGFPNA-AAFSASS 1572
Cdd:cd21688     2 TKKVLVTVDGVNFRTIVVTTGDTYGQQL-GPVYLDGADVTKGKPDNHEGETFFVlpSTPDKAALEYYGFLDPsFLGRYLS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1573 HDAYKFDVVTHNNFIVHKQTDNNCWVNAICLALQRLKPTWKFPGVKSLWDVFLTRKTAGFVHMLYHISGLKKGQPGDAEL 1652
Cdd:cd21688    81 TLAHKWKVKVVDGLRSLKWSDNNCYVSAVILALQQLKIKFKAPALQEAWNKFLGGDPARFVALIYASGNKTVGEPGDVRE 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1653 TLHKLGELMVSDSiVTITHTTACDKCAKIENFTGPVVAAPLMIY--------GTDETCVHGVSVNVKVTSIRGTVAITSL 1724
Cdd:cd21688   161 TLTHLLQHADLSS-ATRVLRVVCKHCGIKTTTLTGVEAVMYVGAlsyddlktGVSIPCPCGGEWTVQVIQQESPFLLLSA 239

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 240015189 1725 IGPVVGDVIDAT--GYICYTGLNSRGHYTYYDNRN-GLMVDAEK 1765
Cdd:cd21688   240 APPAEYKLQQDTfvAANVFTGNTNVGHYTHVTAKElLQKFDGAK 283

deltaCoV_Nsp10

cd21903

deltacoronavirus non-structural protein 10; This model represents the non-structural protein ...

3882-4009

2.25e-36

deltacoronavirus non-structural protein 10; This model represents the non-structural protein 10 (Nsp10) of deltacoronaviruses, including Thrush coronavirus HKU12-600 and Wigeon coronavirus HKU20. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9, and Nsp10 form functional complexes with CoV core enzymes and thereby stimulate replication. Coronaviruses cap their mRNAs; RNA cap methylation may involve at least three proteins: Nsp10, Nsp14, and Nsp16. Nsp10 serves as a cofactor for both Nsp14 and Nsp16. Nsp14 consists of 2 domains with different enzymatic activities: an N-terminal ExoN domain and a C-terminal cap (guanine-N7) methyltransferase (N7-MTase) domain. The association of Nsp10 with Nsp14 enhances Nsp14's exoribonuclease (ExoN) activity, and not its N7-Mtase activity. ExoN is important for proofreading and therefore, the prevention of lethal mutations. The Nsp10/Nsp14 complex hydrolyzes double-stranded RNA in a 3' to 5' direction as well as a single mismatched nucleotide at the 3'-end, mimicking an erroneous replication product, and may function in a replicative mismatch repair mechanism. Nsp16 Cap-0 specific (nucleoside-2'-O-)-methyltransferase (2'OMTase) acts sequentially to Nsp14 MTase in RNA capping methylation and methylates the RNA cap at the ribose 2'-O position; it catalyzes the conversion of the cap-0 structure on m7GpppA-RNA to a cap-1 structure. The association of Nsp10 with Nsp16 enhances Nsp16's 2'OMTase activity, possibly through enhanced RNA binding affinity. Additionally, transmissible gastroenteritis virus (TGEV) Nsp10, Nsp16 and their complex can interact with DII4, which normally binds to Notch receptors; this interaction may disturb Notch signaling. Nsp10 also binds 2 zinc ions with high affinity.

Pssm-ID: 409328 Cd Length: 128 Bit Score: 135.37 E-value: 2.25e-36

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3882 GKPTEHPSNSGLLTLCAFAPDPAKAYVDAVKRGMQPVTNCVKMLSNgAGNGMAVTNGVESNTQQDSYGGASVCIYCRCHV 3961
Cdd:cd21903     2 GTQIEYQENASLLTYLAFAVDPKEAYLKHLADGGKPIQGCIQMIAP-LGPGFAVTTKPQPNEHQYSYGGASICLYCRAHI 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 240015189 3962 EHPAIDGLCRFKGKFVQVPTgTQDPIRFCIENEICVVCGCWLNNGCMC 4009
Cdd:cd21903    81 PHPGVDGRCPYKGRFVHIDK-DKEPVSFALTHEPCNSCQRWVNYDCTC 127

CoV_Nsp9

cd21881

coronavirus non-structural protein 9; This model represents the non-structural protein 9 (Nsp9) ...

3770-3880

8.72e-34

coronavirus non-structural protein 9; This model represents the non-structural protein 9 (Nsp9) from coronaviruses, including highly pathogenic betacoronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. CoVs utilize a multi-subunit replication/transcription machinery assembled from a set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins. All of these Nsps, except for Nsp1 and Nsp2, are considered essential for transcription, replication, and translation of the viral RNA. Nsp9, with Nsp7, Nsp8, and Nsp10, localizes within the replication complex. Nsp9 is an essential single-stranded RNA-binding protein for CoV replication; it shares structural similarity to the oligosaccharide-binding (OB) fold, which is characteristic of proteins that bind to ssDNA or ssRNA. Nsp9 requires dimerization for binding and orienting RNA for subsequent use by the replicase machinery. CoV Nsp9s have diverse forms of dimerization that promote their biological function, which may help elucidate the mechanism underlying CoVs replication and contribute to the development of antiviral drugs. Generally, dimers are formed via interaction of the parallel alpha-helices containing the protein-protein interaction motif GXXXG at the C-terminus; additionally, the N-finger region may also play a critical role in dimerization as seen in porcine delta coronavirus (PDCoV) Nsp9. As a member of the replication complex, Nsp9 may not have a specific RNA-binding sequence but may act in conjunction with other Nsps as a processivity factor, as shown by mutation studies indicating that Nsp9 is a key ingredient that intimately engages other proteins in the replicase complex to mediate efficient virus transcription and replication.

Pssm-ID: 409329 Cd Length: 111 Bit Score: 127.25 E-value: 8.72e-34

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3770 NNEILPGKLKEKAVKASATiDGDAYGSGKALMASESGKSFIYAFVASDSNLKYVKWE-SNNDLIPIELEAPLRFYVDGVN 3848
Cdd:cd21881     1 NNELSPVALKQMSCAAGTD-QTCTDDEAKAYYNNSKGGRFVLAITSDKPDLKVARFLkEDGGTIYTELEPPCRFVTDVPK 79

                          90       100       110
                  ....*....|....*....|....*....|..
gi 240015189 3849 GPEVKYLYFVKNLNTLRRGAVLGYIGATVRLQ 3880
Cdd:cd21881    80 GPKVKYLYFIKNLNSLNRGMVLGSISATVRLQ 111

TM_Y_MHV-like_Nsp3_C

cd21714

C-terminus of non-structural protein 3, including transmembrane and Y domains, from murine ...

1951-2383

9.38e-32

C-terminus of non-structural protein 3, including transmembrane and Y domains, from murine hepatitis virus and betacoronavirus in the A lineage; This model represents the C-terminus of non-structural protein 3 (Nsp3) from betacoronavirus in the embecovirus subgenus (A lineage), including murine hepatitis virus (MHV) and Human coronavirus HKU1. This conserved C-terminus includes two transmembrane (TM) regions TM1 and TM2, an ectodomain (3Ecto) between the TM1 and TM2 that is glycosylated and located on the lumenal side of the ER, an amphiphatic region (AH1) that is not membrane-spanning, and a large Y domain of approximately 370 residues. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. In MHV and the related Severe acute respiratory syndrome-related coronavirus (SARS-CoV), the TM1, 3Ecto and TM2 domains are important for the papain-like protease (PL2pro) domain to process Nsp3-Nsp4 cleavage. It has also been shown that the interaction of 3Ecto with the lumenal loop of Nsp4 is essential for ER rearrangements in cells infected with SARS-CoV or MHV. The Y domain, located at the cytosolic side of the ER, consists of the Y1 and CoV-Y subdomains, which are conserved in nidovirus and coronavirus, respectively. Functional information about the Y domain is limited; it has been shown that Nsp3 binding to Nsp4 is less efficient without the Y domain.

Pssm-ID: 409662 Cd Length: 555 Bit Score: 134.11 E-value: 9.38e-32

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1951 VKSEVCGNSILCKACLASYDELADFDHLQV---------SWDYKSdpLWNRVMQL--SYFTFLAVFgnnYVRFCLMyfVT 2019
Cdd:cd21714    67 FKSQFCNGSMACQLCLSGFDMLDNYKAIDVvqyevdrrvFFDYTS--VLKLVVELvvSYALYTVWF---YPLFCLI--GL 139

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2020 QYLNLWL-SYFGYVKYSWFLHVINFES------ISVEFVIIVIVFEAVLAL-KHIFFPCNNPSCKTCSKIARQTRIPIQV 2091
Cdd:cd21714   140 QLLTTWLpEFFMLETLHWSVRLFVFLAnmlpahVFLRFYIVVTAMYKIFCLfRHVVYGCSKPGCLFCYKRNRSVRVKCST 219

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2092 VVNGSMKTVYVHANGTGKLCKKHNFYCKNCDSYGFDHTFICDEIVRDLSNSVKQTVYATDKSYQEVTKVECSDGFYR-FY 2170
Cdd:cd21714   220 IVGGMLRYYDVMANGGTGFCSKHQWNCINCDSYKPGNTFITVEAAAELSKELKRPVNPTDVAYYTVTDVKQVGCSMRlFY 299

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2171 VGEEFTAYDyDVKHKKYSSQEVL---KTMFLLDDFIVYSPSGSSLASVRNVCVYFSQLIGRPIKIVNSDLLE-------- 2239
Cdd:cd21714   300 ERDGQRVYD-DVNASLFVDMNGLlhsKVKGVPNTHVVVVENDADKANFLNAAVFYAQSLFRPMLMVDKKLITtantgtsv 378

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2240 -----DLSVDFKGALFNAKKNVIKNSFNV---DVSECKNLEECY--------KACNLDVTFSTFEMA--INNAHRFGILI 2301
Cdd:cd21714   379 sqtmfDVYVDTFLSMFDVDRKSLNSFINTahsSLKEGVQLEKVLdtfigcarKSCSIDSDVDTKCIAksVMSAVAAGLEF 458

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2302 TDRSFNNFWPSKIKpgSSGVSAMDIGKCMTFDAKIVNAKVLTQRGKSVVWLSQDFSALSSTAQKVLVKTFVEEGVNFSLT 2381
Cdd:cd21714   459 TDESCNNLVPTYIK--SDNIVAADLGVLIQNSAKHVQGNVAKAANVACIWSVDAFNQLSSDFQHKLKKACVKTGLKLKLT 536


                  ..
gi 240015189 2382 FN 2383
Cdd:cd21714   537 YN 538

deltaCoV-Nsp6

cd21561

deltacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host ...

3179-3491

1.09e-31

deltacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host cell membranes as part of the viral genome replication and transcription machinery; they induce the formation of double-membrane vesicles in infected cells. CoV non-structural protein 6 (Nsp6), a transmembrane-containing protein, together with Nsp3 and Nsp4, have the ability to induce double-membrane vesicles that are similar to those observed in severe acute respiratory syndrome (SARS) coronavirus-infected cells. By itself, Nsp6 can generate autophagosomes from the endoplasmic reticulum. Autophagosomes are normally generated as a cellular response to starvation to carry cellular organelles and long-lived proteins to lysosomes for degradation. Degradation through autophagy may provide an innate defense against virus infection, or conversely, autophagosomes can promote infection by facilitating the assembly of replicase proteins. In addition to initiating autophagosome formation, Nsp6 also limits autophagosome expansion regardless of how they were induced, i.e. whether they were induced directly by Nsp6, or indirectly by starvation or chemical inhibition of MTOR signaling. This may favor coronavirus infection by compromising the ability of autophagosomes to deliver viral components to lysosomes for degradation.

Pssm-ID: 394847 Cd Length: 296 Bit Score: 127.87 E-value: 1.09e-31

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3179 CDeFTPTEVIRQMyGVNLQSGKVKS----LFYPVMTAIAILFAFW--LEFFMYTpftwinpafvsVILAITTLVSAVLVV 3252
Cdd:cd21561     3 CD-WTPEMVYNQA-PINLQSGVVKKtcmwFFHFLFMAVIFLLAALhvFPVHLYP-----------IVLPVFTILAFLLTL 69

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3253 GIKHKMLFFMSFVMPSVILATAH-NVVWDMTYYesLQALVENVNTTFLPVDMQGVMLALFCVV---VFVTYTIRFFTCKQ 3328
Cdd:cd21561    70 TIKHTVVFTTTYLLPSLLMMVVNaNTFWIPNTY--LRSIYEYVFGSFISERLYGYTVALYILVyaqLAINYTLRTRRYRA 147

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3329 SWFSLFVTTVFVMFNIV-KLLGMIGEPWTDDHILlclvnmltMLISLTTKDWFVVFVSYKVAYYIVVyvmhPAFVQDFGf 3407
Cdd:cd21561   148 TSFISFCMQALQYGYVAhIVYRLLTTPWTEGLLF--------TAFSLLTSHPLLAALSWWLAGRIPL----PLILPDLA- 214

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3408 IKCvsIIYMACGYLFCCYYGILYWVNRFTCMTCGVYQFTVSPAELKYMTANNLSAPKTAYDAMILSVKLMGIGGERNIKI 3487
Cdd:cd21561   215 IRV--IVYYVIGYVMCMRFGLFWLINKFTTIPMGTYKYMVSIEQLKYMMAVKMSPPRNAFEVLWANIRLLGLGGNRNIAV 292


                  ....
gi 240015189 3488 STVQ 3491
Cdd:cd21561   293 STVQ 296

TM_Y_HKU9-like_Nsp3_C

cd21715

C-terminus of non-structural protein 3, including transmembrane and Y domains, from Rousettus ...

2012-2388

1.21e-31

C-terminus of non-structural protein 3, including transmembrane and Y domains, from Rousettus bat coronavirus HKU9 and betacoronavirus in the D lineage; This model represents the C-terminus of non-structural protein 3 (Nsp3) from betacoronavirus in the nobecovirus subgenus (D lineage), including Rousettus bat coronavirus HKU9. This conserved C-terminus includes two transmembrane (TM) regions TM1 and TM2, an ectodomain (3Ecto) between the TM1 and TM2 that is glycosylated and located on the lumenal side of the ER, an amphiphatic region (AH1) that is not membrane-spanning, and a large Y domain of approximately 370 residues. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. In the related betacoronaviruses, Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and murine hepatitis virus (MHV), the TM1, 3Ecto and TM2 domains are important for the papain-like protease (PL2pro) domain to process Nsp3-Nsp4 cleavage. It has also been shown that the interaction of 3Ecto with the lumenal loop of Nsp4 is essential for ER rearrangements in cells infected with SARS-CoV or MHV. The Y domain, located at the cytosolic side of the ER, consists of the Y1 and CoV-Y subdomains, which are conserved in nidovirus and coronavirus, respectively. Functional information about the Y domain is limited; it has been shown that Nsp3 binding to Nsp4 is less efficient without the Y domain.

Pssm-ID: 409663 Cd Length: 526 Bit Score: 133.06 E-value: 1.21e-31

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2012 FCLMYFVTQYL-----NLWLSYFGYvkysWFLHVINFESISVEFVIIVIVFEAVLALKHIFFPCNNPSCKTCSKIARQTR 2086
Cdd:cd21715   106 LAVLHLLVLYLpiplgNSWLVVFLY----YIIRLVPFTSMLRMYIVIAFLWLCYKGFVHVRYGCNNVACLMCYKKNVAKR 181

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2087 IPIQVVVNGSMKTVYVHANGTGKLCKKHNFYCKNCDSYGFDHTFICDEIVRDLSNSVKQTVYATDKSYQEVTKVECSDGF 2166
Cdd:cd21715   182 IECSTVVNGVKRMFYVNANGGTYFCTKHNWNCVSCDTYTVDSTFISRQVALDLSAQFKRPINHTDEAYYEVTSVEVRNGY 261

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2167 YRFYVG-------EEFTAYDYDVKHKKYSSQevLKTMFLLDDFIVYSPSGS-SLASVRNVCVYFSQLIGRPIKIVNSDLL 2238
Cdd:cd21715   262 VYCYFDsdgqrsyERFPMDAFTNVSKLHYSE--LKGAAPAFNVLVFDATNRiEENAVKTAAIYYAQLACKPILLVDKRMV 339

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2239 EDLSVD--FKGALFN--AKKNVIKNSFNVDV------------------------------SECKNLEEcykacnlDVTF 2284
Cdd:cd21715   340 GVVGDDatIAKAMFEayAQNYLLKYSIAMDKvkhlystalqqiasgmtvesvlkvfvgstrAEAKDLES-------DVDT 412

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2285 STFEMAINNAHRFGILITDRSFNNFWPSKIKPGSsgVSAMDIGKCMTFDAKIVNAKVLTQRGKSVVWLSQDFSALSSTAQ 2364
Cdd:cd21715   413 NDLVSCIRLCHQEGWDWTTDSWNNLVPTYIKQDT--LSTLEVGQFMTANARYVNANVAKGAAVNLVWRYADFIKLSESMR 490

                         410       420
                  ....*....|....*....|....
gi 240015189 2365 KVLVKTFVEEGVNFSLTFNAVGSD 2388
Cdd:cd21715   491 RQLRVAARKTGLNLLVTTSSLKAD 514

TM_Y_gammaCoV_Nsp3_C

cd21710

C-terminus of gammacoronavirus non-structural protein 3, including transmembrane and Y domains; ...

1940-2381

5.79e-30

C-terminus of gammacoronavirus non-structural protein 3, including transmembrane and Y domains; This model represents the C-terminus of non-structural protein 3 (Nsp3) from gammacoronavirus, including Infectious bronchitis virus. This conserved C-terminus includes two transmembrane (TM) regions TM1 and TM2, an ectodomain (3Ecto) between the TM1 and TM2 that is glycosylated and located on the lumenal side of the ER, an amphiphatic region (AH1) that is not membrane-spanning, and a large Y domain of approximately 370 residues. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. In the related betacoronaviruses, Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and murine hepatitis virus (MHV), the TM1, 3Ecto and TM2 domains are important for the papain-like protease (PL2pro) domain to process Nsp3-Nsp4 cleavage. It has also been shown that the interaction of 3Ecto with the lumenal loop of Nsp4 is essential for ER rearrangements in cells infected with SARS-CoV or MHV. The Y domain, located at the cytosolic side of the ER, consists of the Y1 and CoV-Y subdomains, which are conserved in nidovirus and coronavirus, respectively. Functional information about the Y domain is limited; it has been shown that Nsp3 binding to Nsp4 is less efficient without the Y domain.

Pssm-ID: 409658 Cd Length: 525 Bit Score: 127.95 E-value: 5.79e-30

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1940 GSVQAYSNSSFVKSEVCGNSILCKACLASYDELADFDH-LQVSWDYKSDPL-----WNRVmqlsYFTFLAVFGNNYVRFC 2013
Cdd:cd21710    46 GPYNDYGKDSFDVLRYCGDDFTCRVCLHDKDSLHLYKHaYSVEQFYKDAVSgisfnWNWL----YLVFLILFVKPVAGFV 121

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2014 LMYFVTQYLNLWLSYF--GYVKYSWFLHVI----NFESISVEFVIIVIVFEAVlalKHIFFpCNNPSCKTCSKIARQTRI 2087
Cdd:cd21710   122 IICYCVKYLVLSSTVLqtGVGFLDWFIQTVfthfNFMGAGFYFWLFYKIYIQV---HHILY-CKDITCEVCKRVARSNRH 197

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2088 PIQVVVNGSMKTVYVHANGTGKLCKKHNFYCKNCDSYGFDHTFICDEIVRDLSNSVKQTVYATDKSYQEVTKVECSDGFy 2167
Cdd:cd21710   198 EVSVVVGGRKQLVHVYTNSGYNFCKRHNWYCRNCDKYGHQNTFMSPEVAGELSEKLKRHVKPTAHAYHVVDDACLVDDF- 276

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2168 rfyVGEEFTAY-----DYDVKHKKYSSQEVLKTMFLL-----------DDFIV-YSPSGSSLASVRNVCVYFSQLIGRPI 2230
Cdd:cd21710   277 ---VNLKYKAAtpgkdGAHSAVKCFSVSDFLKKAVFLkdalkceqisnDSFIVcNTQSAHALEEAKNAAIYYAQYLCKPI 353

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2231 KIVNSDLLEDLSVD-FKGALFNAKKNVIKNSFNVDVSECKnleecYKACNL-DVTFST------FEMAInNAHRFGILIT 2302
Cdd:cd21710   354 LILDQALYEQLVVEpVSKSVVDKVCSILSNIISVDTAALN-----YKAGTLrDALLSVtkdeeaVDMAI-FCHNNDVEYT 427

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2303 DRSFNNFWPS------KIKPgssgvsaMDIGKCMTFDAKIVNAKVltQRGKSVVWLSQDFSALSSTAQKVLVKTFVEEGV 2376
Cdd:cd21710   428 SDGFTNVVPSygidtdKLTP-------RDRGFLINADASIANLRV--KNAPPVVWKFSDLIKLSDSCLKYLISATVKSGG 498


                  ....*
gi 240015189 2377 NFSLT 2381
Cdd:cd21710   499 RFFIT 503

betaCoV_Nsp9

cd21898

betacoronavirus non-structural protein 9; This model represents the non-structural protein 9 ...

3770-3880

2.44e-27

betacoronavirus non-structural protein 9; This model represents the non-structural protein 9 (Nsp9) from betacoronaviruses including highly pathogenic Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. CoVs utilize a multi-subunit replication/transcription machinery assembled from a set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins. All of these Nsps, except for Nsp1 and Nsp2, are considered essential for transcription, replication, and translation of the viral RNA. Nsp9, with Nsp7, Nsp8, and Nsp10, localizes within the replication complex. Nsp9 is an essential single-stranded RNA-binding protein for coronavirus replication; it shares structural similarity to the oligosaccharide-binding (OB) fold, which is characteristic of proteins that bind to ssDNA or ssRNA. Nsp9 requires dimerization for binding and orienting RNA for subsequent use by the replicase machinery. CoV Nsp9s have diverse forms of dimerization that promote their biological function, which may help elucidate the mechanism underlying CoVs replication and contribute to the development of antiviral drugs. Generally, dimers are formed via interaction of the parallel alpha-helices containing the protein-protein interaction motif GXXXG; additionally, the N-finger region may also play a critical role in dimerization as seen in porcine delta coronavirus (PDCoV) Nsp9. As a member of the replication complex, Nsp9 may not have a specific RNA-binding sequence but may act in conjunction with other Nsps as a processivity factor, as shown by mutation studies indicating that Nsp9 is a key ingredient that intimately engages other proteins in the replicase complex to mediate efficient virus transcription and replication.

Pssm-ID: 409331 Cd Length: 111 Bit Score: 109.02 E-value: 2.44e-27

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3770 NNEILPGKLKEKAVKA-----SATIDGDAYGSgkalmASESGKsFIYAFVASDSNLKYVKWE-SNNDLIPIELEAPLRFY 3843
Cdd:cd21898     1 NNELMPQGLKTMVVTAgpdqtACNTPALAYYN-----NVQGGR-MVMAILSDVDGLKYAKVEkSDGGFVVLELDPPCKFL 74

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 240015189 3844 VDGVNGPEVKYLYFVKNLNTLRRGAVLGYIGATVRLQ 3880
Cdd:cd21898    75 VQTPKGPKVKYLYFVKGLNNLHRGQVLGTIAATVRLQ 111

deltaCoV_Nsp8

cd21833

deltacoronavirus non-structural protein 8; This model represents the non-structural protein 8 ...

3575-3733

1.65e-24

deltacoronavirus non-structural protein 8; This model represents the non-structural protein 8 (Nsp8) region of deltacoronaviruses that include White-eye coronavirus HKU16 and Quail coronavirus UAE-HKU30, among others. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9, and Nsp10 form functional complexes with CoV core enzymes and thereby stimulate replication. Most importantly, a complex of Nsp8 with Nsp7 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the genes encoding Nsp8 and Nsp7 have been shown to delay virus growth. Nsp8 and Nsp7 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp8 with Nsp7 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp8 has a novel 'golf-club' fold composed of an N-terminal 'shaft' domain and a C-terminal 'head' domain. The shaft domain contains three helices, one of which is very long, while the head domain contains another three helices and seven beta-strands, forming an alpha/beta fold. SARS-CoV Nsp8 forms a 8:8 hexadecameric supercomplex with Nsp7 that adopts a hollow cylinder-like structure with a large central channel and positive electrostatic properties in the cylinder, while Feline infectious peritonitis virus Nsp8 forms a 1:2 heterotrimer with Nsp7. Regardless of their oligomeric structure, the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to the template length.

Pssm-ID: 409260 Cd Length: 189 Bit Score: 103.55 E-value: 1.65e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3575 SVASAYAALPSWIAYEKARADLEEAKKNDVSPQLLKQLTKACNIAKSEFEREVSVQKKLDKMAEQAAASMYKEARAVDRK 3654
Cdd:cd21833     1 AVVDANINLDSYRIYKEADAAYKKSVELNEPPQEQKKKLKAVNIAKAEWEREAASQRKLEKLADAAMKSMYLAERAEDRR 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 240015189 3655 SKIVSAMHSLLFGMLKKLDMSSVNTIIEQARNGVLPLSIIPAASATRLIVVTPNLEVLSKVRQENNVHYAGAIWSIVEV 3733
Cdd:cd21833    81 IKLTSGLTAMLYHMLRRLDSDRVKALFECAKQQILPIHAIVGVSNDNLKVIFNDKESYLQYVDGNTLIYKGVRYTIVKK 159

CoV_NSP2_C

Coronavirus replicase NSP2, C-terminal; This entry corresponds to a presumed domain found at ...

731-879

1.29e-23

Pssm-ID: 465996 Cd Length: 156 Bit Score: 100.03 E-value: 1.29e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189   731 LSNVKIMLGNGVKVF--CDGCNSFAKRLTVSYSKLCDTARKDVEIGGLPFSTfktpASSFIDMKDAIYSVV--------E 800
Cdd:pfam19212    1 LKNAKFTVVNGGIVFvvPKKFKSLVGTLLDLLNKLFDSLVDTVKIAGVKFKA----GGTYYLFSNALVKVVsvklkgkkQ 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189   801 YG-----EAFSFKTANVPVTNSgTIKNDDwsdpILLEPADYVEP-KDNGDVIVIAGYTFYKDEDDHFYPYGSGMVVQKMY 874
Cdd:pfam19212   77 AGlkgakEATVFVGATVPVTPT-RVEVVT----VELEEVDYVPPpVVVGYVVVIDGYAFYKSGDEYYPASTDGVVVPPVF 151


                   ....*
gi 240015189   875 NKMGG 879
Cdd:pfam19212  152 KLKGG 156

alpha_betaCoV_Nsp2

cd21511

alpha- and betacoronavirus non-structural protein 2; Coronavirus Nsps are encoded in ORF1a and ...

113-465

4.15e-23

alpha- and betacoronavirus non-structural protein 2; Coronavirus Nsps are encoded in ORF1a and ORF1b. Post infection, the genomic RNA is released into the cytoplasm of the cell and translated into two long polyproteins (pp), pp1a and pp1ab, which are then autoproteolytically cleaved by two viral proteases Nsp3 and Nsp5 into smaller subunits. Nsp2 is one of these subunits. This alpha- and betacoronavirus family includes alphacoronavirus human coronavirus 229E (HCoV-229E) Nsp2, betacoronavirus Severe acute respiratory syndrome coronavirus (SARS-CoV) Nsp2, SARS-CoV-2 Nsp2, and Murine hepatitis virus (MHV) Nsp2 (also known as p65). The function of Nsp2 remains unclear. SARS-CoV Nsp2, rather than playing a role in viral replication, may be involved in altering the host cell environment; deletion of Nsp2 from the SARS-CoV genome results in only a modest reduction in viral titers. It has been shown to interact with two host proteins, prohibitin 1 (PHB1) and PHB2, which have been implicated in cellular functions, including cell-cycle progression, cell migration, cellular differentiation, apoptosis, and mitochondrial biogenesis. MHV Nsp2/p65, different from SARS-CoV Nsp2, may play an important role in the viral life cycle. This family may be distantly related to the gammacoronavirus Avian infectious bronchitis virus (IBV) Nsp2; IBV Nsp2 is a weak protein kinase R (PKR) antagonist, which may suggest that it plays a role in interfering with intracellular immunity.

Pssm-ID: 439197 Cd Length: 399 Bit Score: 105.33 E-value: 4.15e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  113 YVDQYMCGADGKPV---------------IEGEFKDYFGDE-DVIIYEGEEYHCAWLTVRDDKPLCQQTLLTIREI---Q 173
Cdd:cd21511     4 YVDQYGCGPDGKPVecikdlldvakkgscTLSEQLDGIELKnGVYDLRDHEVVIAWYVERKDVPYEKQTIFTIKSAkfgT 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  174 YNLDIP-HKLPNCAI-REVAPPVKKNSKVVLSEEYRKLYDIFGSpfmsngdslnkCFDSLHFIAATLKC-PCGSESSGVG 250
Cdd:cd21511    84 FVGEVPaHVFPLNSIvKEIQPRVKKKKKVTLSGVIRSFYSKASP-----------NECNPITLSALVKCtHCDEKSWQTG 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  251 DWT-GFKTACCGLHGKVK-GVTLGAVKPGDAVVTSMSA-----------GKGVKFFANSVLQYAGDVENVSVWKVIKTFT 317
Cdd:cd21511   153 DFVdGFTCECGAEYLNWKlDAQSSGVLPPGAVVKTQCPacvnretflrgGGRIVYFGGAVYSYVGCINGVAYWVPRASSS 232

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  318 V--NETVCTTDFEGELNDFIKPESTSPVSCSIKRAFITG----EVDDAVHDCIITGKLDLsTNLFGSAN--LLFKKTPWF 389
Cdd:cd21511   233 VgcFHTGVVGKIVPGAWGLGASAQKLTPLTTGAAVVFVLifarTLFAAVGSVPQLQASAP-TILDGIVNasDRLVDAMQF 311

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189  390 -----VQKCGAIFADAWKV---VEELLCSLKLTYKQIYDVVASLCTSAFTIMdyKPVFVVSHSSVKNLVDKCVKI----L 457
Cdd:cd21511   312 sadlvVATTTSAGAAGYVVaglVDLLKPILEWVLSKIGQVCYAGCDVYERVM--AFLNVVVKAAGKTGVLEEDEFptysL 389


                  ....*...
gi 240015189  458 VKAFDVFT 465
Cdd:cd21511   390 VSGFLVGT 397

betaCoV_Nsp7

cd21827

betacoronavirus non-structural protein 7; This model represents the non-structural protein 7 ...

3492-3574

6.02e-23

betacoronavirus non-structural protein 7; This model represents the non-structural protein 7 (Nsp7) of betacoronaviruses including the highly pathogenic Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9 and Nsp10 form functional complexes with CoV core enzymes and stimulate replication. Most importantly, a complex of Nsp7 with Nsp8 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the NSP7- or NSP8-coding region have been shown to delay virus growth. Nsp7 and Nsp8 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp7 with Nsp8 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp7 has a 4-helical bundle conformation which is strongly affected by its interaction with Nsp8, especially where it concerns alpha-helix 4. SARS-CoV Nsp7 forms a 8:8 hexadecameric supercomplex with Nsp8 that adopts a hollow cylinder-like structure with a large central channel and positive electrostatic properties in the cylinder; the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to template length.

Pssm-ID: 409253 Cd Length: 83 Bit Score: 95.20 E-value: 6.02e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3492 SKLTEMKCTNVVLLGLLSKMHVESNSKEWNYCVGLHNEINLCDDPEVVLEKLLALIAFFLSKHNTCDLSDLIDSYFENTT 3571
Cdd:cd21827     1 SKLTDVKCTSVVLLSVLQQLHVESNSKLWAYCVKLHNDILAAKDPTEAFEKFVSLLSVLLSFPGAVDLDALCSELLDNPT 80


                  ...
gi 240015189 3572 ILQ 3574
Cdd:cd21827    81 VLQ 83

alphaCoV_PLPro

alphacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...

1096-1279

6.23e-23

Pssm-ID: 409648 Cd Length: 289 Bit Score: 101.93 E-value: 6.23e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1096 FKTTDLNGKIILKQQDNNCWVNACCYQLQ------AFEFFNhDLWDDFKKGDVMPFVNFCYAALTLKQGDSGDAEHLLeT 1169
Cdd:cd21731    82 FESDIVNGKRVLKQSDNNCWVNAVCLQLQfakptfKSEGLQ-ALWNKFLTGDVAGFVHWLYWITGANKGDPGDAENTL-N 159

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1170 MLNDY--STAKVTLS--AKCGCGVKEIVLERTVFKLTPLRNEFKYGVCGDCKQINmCKFASVEGSGVFVHdrIEKQTPVS 1245
Cdd:cd21731   160 KLSKYlvSSGSVTVErtTGCDSCNSKRTVTTPVVNASVLRSGVDDGVCKHGVKVT-TRVVSVKGTVIITS--VGKPVVSD 236

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 240015189 1246 QFI-VTPTMHAVYTGTIQNGHYMIEDCIHDYCVDG 1279
Cdd:cd21731   237 ALLlLDGVSYTAFSGDVDNGHYTVYDKATGKVYDG 271

TM_Y_deltaCoV_Nsp3_C

cd21711

C-terminus of deltacoronavirus non-structural protein 3, including transmembrane and Y domains; ...

1910-2167

2.39e-22

C-terminus of deltacoronavirus non-structural protein 3, including transmembrane and Y domains; This model represents the C-terminus of non-structural protein 3 (Nsp3) from deltacoronavirus, including Magpie-robin coronavirus HKU18 and Bulbul coronavirus HKU11, among others. This conserved C-terminus includes two transmembrane (TM) regions TM1 and TM2, an ectodomain (3Ecto) between the TM1 and TM2 that is glycosylated and located on the lumenal side of the ER, an amphiphatic region (AH1) that is not membrane-spanning, and a large Y domain of approximately 370 residues. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. In the related betacoronaviruses, Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and murine hepatitis virus (MHV), the TM1, 3Ecto and TM2 domains are important for the papain-like protease (PL2pro) domain to process Nsp3-Nsp4 cleavage. It has also been shown that the interaction of 3Ecto with the lumenal loop of Nsp4 is essential for ER rearrangements in cells infected with SARS-CoV or MHV. The Y domain, located at the cytosolic side of the ER, consists of the Y1 and CoV-Y subdomains, which are conserved in nidovirus and coronavirus, respectively. Functional information about the Y domain is limited; it has been shown that Nsp3 binding to Nsp4 is less efficient without the Y domain.

Pssm-ID: 409659 Cd Length: 490 Bit Score: 104.02 E-value: 2.39e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1910 YAKLVLLLIALYHFFYLFVSIPL--------VHKLACSG------SVQAYSNSSFvksevCGNSILCKACLASYDELADF 1975
Cdd:cd21711     2 FYSAQTIFVSLAPFLMLPAVASLlssgytigTYLYAKTGlpcyynATQHYDYNSF-----CAGDLTCQACFDGQDSLHLY 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1976 DHLQVSW------DYKsdpLWNRVMQLSYF-------TFLAVFGNNYVRFCLMYFVTQYLNlwlsyfgyvkYSWFLHVIn 2042
Cdd:cd21711    77 KHLRVNQqpvqttDYT---VYALSIVLLLAnptlvlgTLLVVFFVNFYGVQIPFYGTLQLD----------YQNTLVMV- 142

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 2043 fesISVEFVIIVIVFeavlaLKHIFFPCNNPSCKTCSKIARQTRIPIQVVVNGSMKTVYVHANGTGKLCKKHNFYCKNCD 2122
Cdd:cd21711   143 ---FSVYYFYKVMKF-----FRHLAKGCKKPTCSICAKKRIPPTITVETVVQGRKYPSVIETNGGFNICKEHNFYCKNCD 214

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 240015189 2123 SYGFDHTFICDEIVrDLSNSVKQTVYATDKSYQEVTKVECSDGFY 2167
Cdd:cd21711   215 SQTPGTFIPTEAVE-SLSRKTRLSVKPTAPAYLLARDVECQTDVV 258

gammaCoV-Nsp6

cd21559

gammacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host ...

3187-3491

2.61e-22

gammacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host cell membranes as part of the viral genome replication and transcription machinery; they induce the formation of double-membrane vesicles in infected cells. CoV non-structural protein 6 (Nsp6), a transmembrane-containing protein, together with Nsp3 and Nsp4, have the ability to induce double-membrane vesicles that are similar to those observed in severe acute respiratory syndrome (SARS) coronavirus-infected cells. By itself, Nsp6 can generate autophagosomes from the endoplasmic reticulum. Autophagosomes are normally generated as a cellular response to starvation to carry cellular organelles and long-lived proteins to lysosomes for degradation. Degradation through autophagy may provide an innate defense against virus infection, or conversely, autophagosomes can promote infection by facilitating the assembly of replicase proteins. In addition to initiating autophagosome formation, Nsp6 also limits autophagosome expansion regardless of how they were induced, i.e. whether they were induced directly by Nsp6, or indirectly by starvation or chemical inhibition of MTOR signaling. This may favor coronavirus infection by compromising the ability of autophagosomes to deliver viral components to lysosomes for degradation.

Pssm-ID: 394845 Cd Length: 307 Bit Score: 100.61 E-value: 2.61e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3187 VIRQMYGVNLQSGKVK------------SLFYPVMTAIAILFAFWLEFFMYtpftwinpafvsviLAITTLVSAVLV-VG 3253
Cdd:cd21559     3 VFNQVGGVRLQSSFVKkatswfwsrcvlACFLFVLCAIVLFTAVPLKYYVH--------------AAVILLVAVLFIsFT 68

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3254 IKHKMLFFMSFVMP---SVILATAHNV--VWDMTYYESLQALVE----NVNTTFLPVDMQGVMLALFCVVVFVTYTIRFF 3324
Cdd:cd21559    69 VKHVMAFMDTFLLPtlcTVIIGVCAEVpfIYNTLISQVVIFFSQwydpVVFDTVVPWMFLPLVLYTAFKCVQGCYSINSF 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3325 TCKQSWFSLFVTTVFVMFNIVkllgMIGEPWTDDHILLCLVNMLTMLISLTTKDWFVVFVSYKVAYYiVVYVMHPAFVQD 3404
Cdd:cd21559   149 STSLLVLYQFMKLGFVIYTSS----NTLTAYTEGNWELFFELVHTTVLANFSSNSLIGLIVFKIAKW-MLYYCNATYFNS 223

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 3405 FgfikcVSIIYMAC--GYLFCCYYGILYWVNRFTCMTCGVYQFTVSPAELKYMTANNLSAPKTAYDAMILSVKLMGIGGE 3482
Cdd:cd21559   224 Y-----VLMAVMVNviGWLFTCYFGLYWWLNKVFGLTLGKYNYKVSVEQYKYMCLHKIRPPKSVWDVFSTNMLIQGIGGE 298


                  ....*....
gi 240015189 3483 RNIKISTVQ 3491
Cdd:cd21559   299 RVLPIATVQ 307

A1pp

smart00506

Appr-1"-p processing enzyme; Function determined by Martzen et al. Extended family detected by ...

1338-1467

6.63e-21

Appr-1"-p processing enzyme; Function determined by Martzen et al. Extended family detected by reciprocal PSI-BLAST searches (unpublished results, and Pehrson _ Fuji).

Pssm-ID: 214701 Cd Length: 133 Bit Score: 91.21 E-value: 6.63e-21

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189   1338 RISFYQGELDVLinflEPDVVVNAANGDLRHLGGVAKAIDNFTGGKLTKRSkdYLKSNK-SIAPGNAVLFEN-VLEHLSV 1415
Cdd:smart00506    1 ILKVVKGDITKP----RADAIVNAANSDGAHGGGVAGAIARAAGKALSKEE--VRKLAGgECPVGTAVVTEGgNLPAKYV 74

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|....*....
gi 240015189   1416 LNAVGPRNGDSRVEG--KLCNVYK-----AIAKCDGKILTPLISVGIFNVKLEVSLQCL 1467
Cdd:smart00506   75 IHAVGPRASGHSKEGfeLLENAYRnclelAIELGITSVALPLIGTGIYGVPKDRSAQAL 133

betaCoV_PLPro

cd21732

betacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...

1496-1756

4.19e-20

betacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) found in non-structural protein 3 (Nsp3) of betacoronavirus, including highly pathogenic betacoronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. PLPro is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. PLPro, which belongs to the MEROPS peptidase C16 family, participates in the proteolytic processing of the N-terminal region of the replicase polyprotein; it can cleave Nsp1|Nsp2, Nsp2|Nsp3, and Nsp3|Nsp4 sites and its activity is dependent on zinc. In SARS-CoV and murine hepatitis virus (MHV), the C-terminal non-structural protein 3 region spanning transmembrane regions TM1 and TM2 with 3Ecto domain in between, are important for the PL2pro domain to process Nsp3-Nsp4 cleavage. Besides cleaving the polyproteins, PLPro also possesses a related enzymatic activity to promote virus replication: deubiquitinating (DUB) and de-ISGylating activities. Both, ubiquitin (Ub) and Ub-like interferon-stimulated gene product 15 (ISG15), are involved in preventing viral infection; coronaviruses utilize Ubl-conjugating pathways to counter the pro-inflammatory properties of Ubl-conjugated host proteins via the action of PLPro, which processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. The Nsp3 PLPro domain of many of these CoVs has also been shown to antagonize host innate immune induction of type I interferon by interacting with IRF3 and blocking its activation. Interactions of SARS-CoV and MERS-CoV with antiviral interferon (IFN) responses of human cells are remarkably different; high-dose IFN treatment (type I and type III) shows MERS-CoV was substantially more IFN sensitive than SARS-CoV. This may be due to differences in the architecture of the oxyanion hole and of the S3 as well as the S5 specificity sites, despite the overall structures of SARS-CoV and MERS-CoV PLPro being similar.

Pssm-ID: 409649 Cd Length: 304 Bit Score: 94.19 E-value: 4.19e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1496 TIPVKVTEDTVNQKRVSVALDKTYGEQLkGTVVIKDKDVTNQLPSVSDAGeKVVKALDVDWNA-------YYGFPN---- 1564
Cdd:cd21732     2 TIEVLTTVDGVNFRTVLVNNGETFGKQL-GNVFCDGVDVTKTKPSAKYEG-KVLFQADNLSAEeleaveyYYGFDDptfl 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1565 AAAFSASSHDAyKFDVVTHNNFIVHKQTDNNCWVNAICLALQRLKPTWKFPGVKSLWDVFLTRKTAGFVHMLYHISGLKK 1644
Cdd:cd21732    80 LRYYSALAHVK-KWKFVVVDGYFSLKQADNNCYLNAACLMLQQLDLKFNTPALQEAYYEFRAGDPLRFVALVLAYGNFTF 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1645 GQPGDAELTLHKL---GELmVSDSIVTithTTACDKC-AKIENFTGpvVAApLMIYGT----------DETCVHGVSVNV 1710
Cdd:cd21732   159 GEPDDARDFLRVVlshADL-VSARRVL---EEVCKVCgVKQEQRTG--VDA-VMYFGTlslddlykgyTIDCSCGRKAIR 231

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*....
gi 240015189 1711 KVTSIRGTVAITSliGPVVGDVIDATGYIC---YTGLNSRGHYTYYDNR 1756
Cdd:cd21732   232 YLVEQVPPFLLMS--NTPTEVPLPTGDFVAanvFTGDESVGHYTHVKNK 278

Macro_Af1521_BAL-like

cd02907

macrodomain, Af1521-like family; Macrodomains are found in a variety of proteins with diverse ...

1338-1473

3.34e-18

macrodomain, Af1521-like family; Macrodomains are found in a variety of proteins with diverse cellular functions, as a stand-alone domain or in combination with other domains like in histone macroH2A and some PARPs (poly ADP-ribose polymerases). Macrodomains can recognize ADP-ribose (ADPr) in both its free and protein-linked forms, in related ligands, such as O-acyl-ADP-ribose (OAADPr), and even in ligands unrelated to ADPr. The macrodomains in this family show similarity to Af1521, a protein from Archaeoglobus fulgidus containing a stand-alone macrodomain. Af1521 binds ADP-ribose and exhibits phosphatase activity toward ADP-ribose-1"-monophosphate (Appr-1"-p). Also included in this family are the N-terminal (or first) macrodomains of BAL (B-aggressive lymphoma) proteins which contain multiple macrodomains, such as the first macrodomain of mono-ADP-ribosyltransferase PARP14 (PARP-14, also known as ADP-ribosyltransferase diphtheria toxin-like 8, ATRD8, B aggressive lymphoma protein 2, or BAL2). Most BAL proteins also contain a C-terminal PARP active site and are also named as PARPs. Human BAL1 (or PARP-9) was originally identified as a risk-related gene in diffuse large B-cell lymphoma that promotes malignant B-cell migration. Some BAL family proteins exhibit PARP activity. Poly (ADP-ribosyl)ation is an immediate DNA-damage-dependent post-translational modification of histones and other nuclear proteins. BAL proteins may also function as transcriptional repressors.

Pssm-ID: 394877 [Multi-domain] Cd Length: 158 Bit Score: 84.46 E-value: 3.34e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240015189 1338 RISFYQG---ELDVlinflepDVVVNAANGDLRHLGGVAKAIDNFTGGKLTKRSKDYLKSNKSIAPGNAVlfenvleHLS 1414
Cdd:cd02907     3 KVSVYKGditKEKV-------DAIVNAANERLKHGGGVAGAISKAGGPEIQEECDKYIKKNGKLRVGEVV-------VTS 68

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 240015189 1415 --------VLNAVGPR---NGDSRVEGKLCN-VYKAIAKCDGKILT----PLISVGIFNVKLEVSLQCLLKTVTD 1473
Cdd:cd02907    69 agklpckyVIHAVGPRwsgGSKEECEDLLYKaVLNSLEEAEELKATsiaiPAISSGIFGFPLDLCAEAIVEAIKD 143

CoV_peptidase