conserved catalytic core domain of RNA-dependent RNA polymerase (RdRp) from the positive-sense single-stranded RNA [(+)ssRNA] viruses and closely related viruses; This family contains the catalytic core domain of RdRp of RNA viruses which belong to Group IV of the Baltimore classification system, and are a group of related viruses that have positive-sense (+), single-stranded (ss) genomes made of ribonucleic acid (RNA). RdRp (also known as RNA replicase) catalyzes the replication of RNA from an RNA template; specifically, it catalyzes the synthesis of the RNA strand complementary to a given RNA template. The Baltimore Classification is divided into 7 classes, 3 of which include RNA viruses: Group IV (+) RNA viruses, Group III double-stranded (ds) RNA viruses, and Group V negative-sense (-) RNA viruses. Baltimore groups of viruses differ with respect to the nature of their genome (i.e., the nucleic acid form that is packaged into virions) and correspond to distinct strategies of genome replication and expression. (+) viral RNA is similar to mRNA and thus can be immediately translated by the host cell. (+)ssRNA viruses can also produce (+) copies of the genome from (-) strands of an intermediate dsRNA genome. This acts as both a transcription and a replication process since the replicated RNA is also mRNA. RdRps belong to the expansive class of polymerases containing so-called palm catalytic domains along with the accessory fingers and thumb domains. All RdRps also have six conserved structural motifs (A-F), located in its majority in the palm subdomain (A-E motifs) and the F motif is located on the finger subdomain. All these motifs have been shown to be implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides. In addition to Group IV viruses, this model also includes Picobirnaviruses (PBVs), members of the family Picobirnaviridae of dsRNA viruses (Baltimore classification Group III), which are bi-segmented dsRNA viruses. The phylogenetic tree of the RdRps of RNA viruses (realm Riboviria) showed that picobirnaviruses are embedded in the branch of diverse (+)RNA viruses; sometimes they are collectively referred to as the picornavirus supergroup. RdRps of members of the family Permutatetraviridae, a distinct group of RNA viruses that encompass a circular permutation within the RdRp palm domain, are not included in this model.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1154255739   1 KFYSLHLKIPSTVGITKFYGGWDRLLESLPDGWIYCDADGSQFDSSLTPYLLNAVLEMRLSFMEDWDVGEQMLKNLYTEI 80
Cdd:cd23175    49 QFYSLHLKAPWTVGITKFYGGWDKLLRKLPDGWVYCDADGSQFDSSLTPYLINAVLRIRLHFMEDWDIGEQMLRNLYTEI 128

                          90
                  ....*....|.
gi 1154255739  81 VYTPILTPDGT 91
Cdd:cd23175   129 VYTPILTPDGT 139

catalytic core domain of RNA-dependent RNA polymerase (RdRp) in the family Potyviridae of positive-sense single-stranded RNA [(+)ssRNA] viruses; This group contains the catalytic core domain of RdRp of RNA viruses belonging to the family Potyviridae, order: Patatavirales. Potyviridae, is the largest family of RNA plant viruses, members of which have (+)ssRNA genomes and flexuous filamentous particles. The family is divided into eight genera: Brambyvirus, Bymovirus, Ipomovirus, Macluravirus, Poacevirus, Potyvirus, Rymovirus, and Tritimovirus. Most genomes are monopartite but those of members of the genus Bymovirus are bipartite. Some members cause serious disease epidemics in cultivated plants. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1154255739   1 KFYSLHLKIPSTVGITKFYGGWDRLLESLPDGWIYCDADGSQFDSSLTPYLLNAVLEMRLSFMEDWDVGEQMLKNLYTEI 80
Cdd:cd23175    49 QFYSLHLKAPWTVGITKFYGGWDKLLRKLPDGWVYCDADGSQFDSSLTPYLINAVLRIRLHFMEDWDIGEQMLRNLYTEI 128

                          90
                  ....*....|.
gi 1154255739  81 VYTPILTPDGT 91
Cdd:cd23175   129 VYTPILTPDGT 139

catalytic core domain of RNA-dependent RNA polymerase (RdRp) in the family Potyviridae of positive-sense single-stranded RNA [(+)ssRNA] viruses; This group contains the catalytic core domain of RdRp of RNA viruses belonging to the family Potyviridae, order: Patatavirales. Potyviridae, is the largest family of RNA plant viruses, members of which have (+)ssRNA genomes and flexuous filamentous particles. The family is divided into eight genera: Brambyvirus, Bymovirus, Ipomovirus, Macluravirus, Poacevirus, Potyvirus, Rymovirus, and Tritimovirus. Most genomes are monopartite but those of members of the genus Bymovirus are bipartite. Some members cause serious disease epidemics in cultivated plants. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1154255739   1 KFYSLHLKIPSTVGITKFYGGWDRLLESLPDGWIYCDADGSQFDSSLTPYLLNAVLEMRLSFMEDWDVGEQMLKNLYTEI 80
Cdd:cd23175    49 QFYSLHLKAPWTVGITKFYGGWDKLLRKLPDGWVYCDADGSQFDSSLTPYLINAVLRIRLHFMEDWDIGEQMLRNLYTEI 128

                          90
                  ....*....|.
gi 1154255739  81 VYTPILTPDGT 91
Cdd:cd23175   129 VYTPILTPDGT 139

RNA_dep_RNAP: RNA-dependent RNA polymerase (RdRp) is an essential protein encoded in the genomes of all RNA containing viruses with no DNA stage. RdRp catalyzes synthesis of the RNA strand complementary to a given RNA template. RdRps of many viruses are products of processing of polyproteins. Some RdRps consist of one polypeptide chain, and others are complexes of several subunits. The domain organization and the 3D structure of the catalytic center of a wide range of RdRps, including those with a low overall sequence homology, are conserved. The catalytic center is formed by several motifs containing a number of conserved amino acid residues. This subfamily represents the RNA-dependent RNA polymerases from all positive-strand RNA eukaryotic viruses with no DNA stage.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1154255739   1 KFYSLHLKIPSTVGITKFYGGWDRLLESL-PDGWIYCDADGSQFDSSLTPYLLNAVLEMRLSFMEDWDvgEQMLKNLYTE 79
Cdd:cd01699    63 KLMKNRGGLPIAVGINPYSRDWTILANKLrSFSPVAIALDYSRFDSSLSPQLLEAEHSIYNALYDDDD--ELERRNLLRS 140

                          90
                  ....*....|..
gi 1154255739  80 IVYTPilTPDGT 91
Cdd:cd01699   141 LTNNS--LHIGF 150

catalytic core domain of RNA-dependent RNA polymerase (RdRp) in the family Astroviridae of positive-sense single-stranded RNA [(+)ssRNA] viruses; This group contains the catalytic core domain of RdRp of RNA viruses belonging to the family Astroviridae, order, Stellavirales. Astrovirus has a non-segmented, (+)ssRNA genome within a non-enveloped icosahedral capsid. The family Astroviridae comprises two genera, Mamastrovirus, which infect mammals, and Avastrovirus, which infect birds. Astroviruses have been isolated from stools from a wide variety of mammals and birds. Human astroviruses have been shown to be an important cause of gastroenteritis in young children. Duck astrovirus causes an often-fatal hepatitis in ducklings. Astroviruses infecting turkeys, guinea fowl and chickens affect multiple organs, including the kidney and thymus. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1154255739  13 VGITKFYGGWDRLLESLPD-GWIYCDADGSQFDSSLTPYLLNAVLEMRLSFM------EDWDVGEQMLKNLyteiVYTPI 85
Cdd:cd23172    59 VGWSPFYGGFDARVRRLGSkGNYFVEFDWTRFDGTIPAELFRHIRKLRWSFLdpekteENRKVYDWYVHNL----LNRYV 134

                  ....*
gi 1154255739  86 LTPDG 90
Cdd:cd23172   135 LLPTG 139

human coronavirus HKU1 RNA-dependent RNA polymerase, also known as non-structural protein 12, and similar proteins from betacoronaviruses in the A lineage: responsible for replication and transcription of the viral RNA genome; This group contains the RNA-dependent RNA polymerase (RdRp) of human coronavirus HKU1, murine hepatitis virus, and similar proteins from betacoronaviruses in the embecovirus subgenera (A lineage). 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. A key component, the RNA-dependent RNA polymerase (RdRp, also known as Nsp12), catalyzes the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of CoV, possibly interacting with its co-factors, Nsp7 and Nsp8. RdRp is therefore considered a primary target for nucleotide analog antiviral inhibitors such as remdesivir. Nsp12 contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1154255739   9 IPSTVGITKFYGGWDRLLESLPD--------GWIY--CD 37
Cdd:cd21593   578 VPVVIGTTKFYGGWDDMLRRLIKdvdnpvlmGWDYpkCD 616

gammacoronavirus RNA-dependent RNA polymerase, also known as non-structural protein 12: responsible for replication and transcription of the viral RNA genome; This subfamily contains the RNA-dependent RNA polymerase (RdRp) of gammacoronaviruses, including the RdRp of avian infectious bronchitis virus (IBV) and similar proteins. 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. A key component, the RNA-dependent RNA polymerase (RdRp, also known as Nsp12), catalyzes the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of CoV, possibly interacting with its co-factors, Nsp7 and Nsp8. RdRp is therefore considered a primary target for nucleotide analog antiviral inhibitors such as remdesivir. Nsp12 contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides.

                          10        20
                  ....*....|....*....|...
gi 1154255739  10 PSTVGITKFYGGWDRLLESLPDG 32
Cdd:cd21587   585 PVVIGTTKFYGGWDNMLRNLIQG 607

coronavirus RNA-dependent RNA polymerase, also known as non-structural protein 12: responsible for replication and transcription of the viral RNA genome; This family contains the RNA-dependent RNA polymerase of alpha-, beta-, gamma-, delta-coronaviruses, including three highly pathogenic human coronaviruses (CoVs) such as Middle East respiratory syndrome (MERS)-related CoV, Severe acute respiratory syndrome (SARS) CoV, and SARS-CoV-2, also known as 2019 novel CoV (2019-nCoV) or COVID-19 virus. 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. A key component, the RNA-dependent RNA polymerase (RdRp, also known as Nsp12), catalyzes the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of CoV, possibly interacting with its co-factors, Nsp7 and Nsp8. RdRp is therefore considered a primary target for nucleotide analog antiviral inhibitors such as remdesivir, which shows potential for the treatment of SARS-CoV-2 viral infections. The structure of SARS-CoV-2 Nsp12 contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1154255739  10 PSTVGITKFYGGWDRLLESLPD--------GWIY--CD 37
Cdd:cd21530   582 TVVIGTTKFYGGWDNMLRTLYSgvenpmlmGWDYpkCD 619

Middle East respiratory syndrome-related coronavirus RNA-dependent RNA polymerase, also known as non-structural protein 12, and similar proteins from betacoronaviruses in the C lineage: responsible for replication and transcription of the viral RNA genome; This group contains the RNA-dependent RNA polymerase (RdRp) of Middle East respiratory syndrome (MERS)-related CoV, bat-CoV HKU5, and similar proteins from betacoronaviruses in the merbecovirus subgenera (C lineage). 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. A key component, the RNA-dependent RNA polymerase (RdRp, also known as Nsp12), catalyzes the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of CoV, possibly interacting with its co-factors, Nsp7 and Nsp8. RdRp is therefore considered a primary target for nucleotide analog antiviral inhibitors such as remdesivir, which has been shown to potently inhibit MERS RdRp. Nsp12 contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides.

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1154255739  13 VGITKFYGGWDRLLESL------PD--GWIY--CD 37
Cdd:cd21592   588 IGTTKFYGGWDFMLKTLykdvdnPHlmGWDYpkCD 622