receptor-binding domain of the S1 subunit of coronavirus spike (S) proteins; This family contains the receptor-binding domain (RBD) of the S1 subunit of coronavirus (CoV) spike (S) proteins from three highly pathogenic human coronaviruses (CoVs), including Middle East respiratory syndrome coronavirus (MERS-CoV), Severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV), and SARS coronavirus 2 (SARS-CoV-2), also known as a 2019 novel coronavirus (2019-nCoV), as well as S proteins from related coronaviruses. The CoV S protein is an envelope glycoprotein that plays the most important role in viral attachment, fusion, and entry into host cells, and serves as a major target for the development of neutralizing antibodies, inhibitors of viral entry, and vaccines. It is synthesized as a precursor protein that is cleaved into an N-terminal S1 subunit (~700 amino acids) and a C-terminal S2 subunit (~600 amino acids) that mediates attachment and membrane fusion, respectively. Three S1/S2 heterodimers assemble to form a trimer spike protruding from the viral envelope. The S1 subunit contains a receptor-binding domain (RBD), while the S2 subunit contains a hydrophobic fusion peptide and two heptad repeat regions. S1 contains two structurally independent domains, the N-terminal domain (NTD) and the C-terminal domain (C-domain). Depending on the virus, either the NTD or the C-domain can serve as the receptor-binding domain (RBD). While the RBD of mouse hepatitis virus (MHV) is located at the NTD, most CoVs, including SARS-CoV-2, SARS-CoV and MERS-CoV use the C-domain to bind their receptors. MHV uses mouse carcinoembryonic antigen related cell adhesion molecule 1a (mCEACAM1a) as the receptor, and the receptors for SARS-CoV and MERS-CoV are human angiotensin-converting enzyme 2 (ACE2) and human dipeptidyl peptidase 4 (DPP4), respectively. Recent studies found that the RBD of SARS-CoV-2 S protein binds strongly to human and bat angiotensin-converting enzyme 2 (ACE2) receptors. Moreover, SARS-CoV-2 RBD exhibited significantly higher binding affinity to the ACE2 receptor than SARS-CoV RBD. Due to the key role of the S protein RBD in viral attachment, it is the major target for antibody-mediated neutralization. This model corresponds to the S1 subunit C-domain that serves as the RBD for most CoVs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556015081   1 VADYSVLYNSTSFSTFKCYGVSATKLNDLCFSNVYADSFVVKGDDVRQIAPGQTGVIADYNYKLPDDFTGCVLAWNTRNI 80
Cdd:cd21481   44 VADYSVLYNSTFFSTFKCYGVSATKLNDLCFSNVYADSFVVKGDDVRQIAPGQTGVIADYNYKLPDDFMGCVLAWNTRNI 123

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556015081  81 DATQTGNYNYKYRSLRHGKLRPFERDISNVPFSPDGKPCTPPAFNCYWPLNDYGFYITNGIGYQPYRVVVLSFELLNAPA 160
Cdd:cd21481  124 DATSTGNYNYKYRYLRHGKLRPFERDISNVPFSPDGKPCTPPALNCYWPLNDYGFYTTTGIGYQPYRVVVLSFELLNAPA 203

                        170
                 ....*....|....*....
gi 556015081 161 TVCGPKLSTDLIKNQCVNF 179
Cdd:cd21481  204 TVCGPKLSTDLIKNQCVNF 222

receptor-binding domain of the S1 subunit of severe acute respiratory syndrome-related coronavirus Spike (S) protein; This group contains the receptor-binding domain of the S1 subunit of the spike (S) protein from severe acute respiratory syndrome-related coronavirus (SARS-CoV) and similar coronaviruses. The CoV S protein is an envelope glycoprotein that plays the most important role in viral attachment, fusion, and entry into host cells, and serves as a major target for the development of neutralizing antibodies, inhibitors of viral entry, and vaccines. It is synthesized as a precursor protein that is cleaved into an N-terminal S1 subunit (~700 amino acids) and a C-terminal S2 subunit (~600 amino acids) that mediates attachment and membrane fusion, respectively. Three S1/S2 heterodimers assemble to form a trimer spike protruding from the viral envelope. The S1 subunit contains a receptor-binding domain (RBD), while the S2 subunit contains a hydrophobic fusion peptide and two heptad repeat regions. S1 contains two structurally independent domains, the N-terminal domain (NTD) and the C-terminal domain (C-domain). Depending on the virus, either the NTD or the C-domain can serve as the receptor-binding domain (RBD). While the RBD of mouse hepatitis virus (MHV) is located at the NTD, most CoVs, including SARS-CoV use the C-domain to bind their receptors. Due to the key role of the S protein RBD in viral attachment, it is the major target for antibody-mediated neutralization. This model corresponds to the S1 subunit C-domain that serves as the RBD for SARS-CoV and most CoVs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556015081   1 VADYSVLYNSTSFSTFKCYGVSATKLNDLCFSNVYADSFVVKGDDVRQIAPGQTGVIADYNYKLPDDFTGCVLAWNTRNI 80
Cdd:cd21481   44 VADYSVLYNSTFFSTFKCYGVSATKLNDLCFSNVYADSFVVKGDDVRQIAPGQTGVIADYNYKLPDDFMGCVLAWNTRNI 123

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556015081  81 DATQTGNYNYKYRSLRHGKLRPFERDISNVPFSPDGKPCTPPAFNCYWPLNDYGFYITNGIGYQPYRVVVLSFELLNAPA 160
Cdd:cd21481  124 DATSTGNYNYKYRYLRHGKLRPFERDISNVPFSPDGKPCTPPALNCYWPLNDYGFYTTTGIGYQPYRVVVLSFELLNAPA 203

                        170
                 ....*....|....*....
gi 556015081 161 TVCGPKLSTDLIKNQCVNF 179
Cdd:cd21481  204 TVCGPKLSTDLIKNQCVNF 222

Coronavirus spike glycoprotein S1, C-terminal; This entry represents a domain found at the C-terminus of the Coronavirus S1 protein. It is found across a range of alpha, beta and gamma coronaviruses. This small all beta stranded domain is known as subdomain 2 in the structure of the porcine epidemic diarrhea virus spike protein.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 556015081  174 NQCVNFNFNGLTGTGVLTPSSKRFqPFQQFGRDVSDFTDSVRDPKTSEILDISPCSF 230
Cdd:pfam19209   1 NVCTDYTIYGITGTGVIRETNSTI-PSGLYYTSSSGDLLGFKNSTTGTVYSVTPCVS 56

receptor-binding domain of the S1 subunit of severe acute respiratory syndrome-related coronavirus Spike (S) protein; This group contains the receptor-binding domain of the S1 subunit of the spike (S) protein from severe acute respiratory syndrome-related coronavirus (SARS-CoV) and similar coronaviruses. The CoV S protein is an envelope glycoprotein that plays the most important role in viral attachment, fusion, and entry into host cells, and serves as a major target for the development of neutralizing antibodies, inhibitors of viral entry, and vaccines. It is synthesized as a precursor protein that is cleaved into an N-terminal S1 subunit (~700 amino acids) and a C-terminal S2 subunit (~600 amino acids) that mediates attachment and membrane fusion, respectively. Three S1/S2 heterodimers assemble to form a trimer spike protruding from the viral envelope. The S1 subunit contains a receptor-binding domain (RBD), while the S2 subunit contains a hydrophobic fusion peptide and two heptad repeat regions. S1 contains two structurally independent domains, the N-terminal domain (NTD) and the C-terminal domain (C-domain). Depending on the virus, either the NTD or the C-domain can serve as the receptor-binding domain (RBD). While the RBD of mouse hepatitis virus (MHV) is located at the NTD, most CoVs, including SARS-CoV use the C-domain to bind their receptors. Due to the key role of the S protein RBD in viral attachment, it is the major target for antibody-mediated neutralization. This model corresponds to the S1 subunit C-domain that serves as the RBD for SARS-CoV and most CoVs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556015081   1 VADYSVLYNSTSFSTFKCYGVSATKLNDLCFSNVYADSFVVKGDDVRQIAPGQTGVIADYNYKLPDDFTGCVLAWNTRNI 80
Cdd:cd21481   44 VADYSVLYNSTFFSTFKCYGVSATKLNDLCFSNVYADSFVVKGDDVRQIAPGQTGVIADYNYKLPDDFMGCVLAWNTRNI 123

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556015081  81 DATQTGNYNYKYRSLRHGKLRPFERDISNVPFSPDGKPCTPPAFNCYWPLNDYGFYITNGIGYQPYRVVVLSFELLNAPA 160
Cdd:cd21481  124 DATSTGNYNYKYRYLRHGKLRPFERDISNVPFSPDGKPCTPPALNCYWPLNDYGFYTTTGIGYQPYRVVVLSFELLNAPA 203

                        170
                 ....*....|....*....
gi 556015081 161 TVCGPKLSTDLIKNQCVNF 179
Cdd:cd21481  204 TVCGPKLSTDLIKNQCVNF 222

receptor-binding domain of the S1 subunit of severe acute respiratory syndrome coronavirus 2 Spike (S) protein; This group contains the receptor-binding domain of the S1 subunit of the spike (S) protein from highly pathogenic human virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as 2019 novel coronavirus (2019-nCoV). The CoV S protein is an envelope glycoprotein that plays the most important role in viral attachment, fusion, and entry into host cells, and serves as a major target for the development of neutralizing antibodies, inhibitors of viral entry, and vaccines. It is synthesized as a precursor protein that is cleaved into an N-terminal S1 subunit (~700 amino acids) and a C-terminal S2 subunit (~600 amino acids) that mediates attachment and membrane fusion, respectively. Three S1/S2 heterodimers assemble to form a trimer spike protruding from the viral envelope. The S1 subunit contains a receptor-binding domain (RBD), while the S2 subunit contains a hydrophobic fusion peptide and two heptad repeat regions. S1 contains two structurally independent domains, the N-terminal domain (NTD) and the C-terminal domain (C-domain). Depending on the virus, either the NTD or the C-domain can serve as the receptor-binding domain (RBD). While RBD of mouse hepatitis virus (MHV) is located at the NTD, most of other CoVs, including SARS-CoV-2 use the C-domain to bind their receptors. Recent studies found that the receptor-binding domain (RBD) of SARS-CoV-2 S protein binds strongly to human and bat angiotensin-converting enzyme 2 (ACE2) receptors. Moreover, SARS-CoV-2 RBD exhibited significantly higher binding affinity to the ACE2 receptor than SARS-CoV RBD. Due to the key role of the S protein RBD in viral attachment, it is the major target for antibody-mediated neutralization. This model corresponds to the S1 subunit C-domain that serves as the RBD for SARS-CoV-2 and most CoVs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556015081   1 VADYSVLYNSTSFSTFKCYGVSATKLNDLCFSNVYADSFVVKGDDVRQIAPGQTGVIADYNYKLPDDFTGCVLAWNTRNI 80
Cdd:cd21480   44 VADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNL 123

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556015081  81 DATQTGNYNYKYRSLRHGKLRPFERDISNVPFSPDGKPCTP-PAFNCYWPLNDYGFYITNGIGYQPYRVVVLSFELLNAP 159
Cdd:cd21480  124 DSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGvEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAP 203

                        170       180
                 ....*....|....*....|
gi 556015081 160 ATVCGPKLSTDLIKNQCVNF 179
Cdd:cd21480  204 ATVCGPKKSTNLVKNKCVNF 223

SD-1 and SD-2 subdomains, the S1/S2 cleavage region, and the S2 fusion subunit of the spike (S) glycoprotein from SARS-CoV-2 (COVID-19) and related betacoronaviruses in the B lineage; This group contains the SD-1 and SD-2 subdomains of the S1 subunit C-terminal domain (C-domain), the S1/S2 cleavage region, and the S2 fusion subunit of the spike (S) glycoprotein from betacoronaviruses in the sarbecovirus subgenus (B lineage), including highly pathogenic human CoVs such as Severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV), and SARS-CoV-2 (also known as a 2019 novel coronavirus or 2019-nCoV). The CoV S protein is an envelope glycoprotein that plays a very important role in viral attachment, fusion, and entry into host cells, and serves as a major target for the development of neutralizing antibodies, inhibitors of viral entry, and vaccines. It is synthesized as a precursor protein that is cleaved into an N-terminal S1 subunit (~700 amino acids) and a C-terminal S2 subunit (~600 amino acids) that mediates attachment and membrane fusion, respectively. Three S1/S2 heterodimers assemble to form a trimer spike protruding from the viral envelope. The S1 subunit contains a receptor-binding domain (RBD), while the S2 subunit contains the coronavirus fusion machinery and is primarily alpha-helical. S1 contains two structurally independent domains, the N-terminal domain (NTD) and the C-domain. The S1 C-domain also contains two subdomains (SD-1 and SD-2), which connect the S1 and S2 subunits. Depending on the virus, either the NTD or the C-domain can serve as the receptor-binding domain (RBD). While the RBD of mouse hepatitis virus (MHV) is located at the NTD, most CoVs, including SARS-CoV-2, SARS-CoV and MERS-CoV use the C-domain to bind their receptors. The S2 subunit comprises the fusion peptide (FP), a second proteolytic site (S2'), followed by an internal fusion peptide (IFP) and two heptad-repeat domains (HR1 and HR2) preceding the transmembrane domain (TM). After binding of the S1 subunit RBD on the virion to its receptor on the target cell, the HR1 and HR2 domains interact with each other to form a six-helix bundle (6-HB) fusion core, bringing viral and cellular membranes into close proximity for fusion and infection. In order to catalyze the membrane fusion reaction, CoV S needs to be primed through cleavage at the S1/S2 and S2' sites. Notably, SARS-CoV-2 has a functional polybasic (furin) cleavage site through the insertion of PRRAR*SV (* indicates the cleavage site) at the S1/S2 interface, which is absent in SARS-CoV and other SARS-related coronaviruses. The region modeled in this cd (SD-1 and SD-2, the S1/S2 cleavage region, and the S2 fusion subunit) plays an essential role in viral entry by initiating fusion of the viral and cellular membranes.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 556015081 181 FNGLTGTGVLTPSSKRFQPFQQFGRDVSDFTDSVRDPKTSEILDISPCSFGGVSVITPGTNTS 243
Cdd:cd22378    1 FNGLTGTGVLTPSSKRFQPFQQFGRDVSDFTDSVRDPKTLEILDISPCSFGGVSVITPGTNAS 63

receptor-binding domain of the S1 subunit of the Spike (S) protein from human coronavirus OC43 and related proteins; This group contains the receptor-binding domain (RBD) of the S1 subunit of the spike (S) protein from several betacoronaviruses including human coronavirus OC43 (HCoV-OC43) and bovine respiratory coronavirus (BCoV), among others. HCoV-OC43 is of zoonotic origin and is endemic in the human population, causing mild respiratory tract infections and possible severe complications or fatalities in young children, the elderly, and immunocompromised individuals. These viruses are related to the zoonotic SARS and MERS betacoronaviruses, which have high fatality rates and pandemic potential. The CoV S protein is an envelope glycoprotein that plays the most important role in viral attachment, fusion, and entry into host cells, and serves as a major target for the development of neutralizing antibodies, inhibitors of viral entry, and vaccines. It is synthesized as a precursor protein that is cleaved into an N-terminal S1 subunit (~700 amino acids) and a C-terminal S2 subunit (~600 amino acids) that mediates attachment and membrane fusion, respectively. Three S1/S2 heterodimers assemble to form a trimer spike protruding from the viral envelope. The S1 subunit contains a receptor-binding domain (RBD), while the S2 subunit contains a hydrophobic fusion peptide and two heptad repeat regions. S1 contains two structurally independent domains, the N-terminal domain (NTD) and the C-terminal domain (C-domain). Depending on the virus, either the NTD or the C-domain can serve as the receptor-binding domain (RBD). While the RBD of mouse hepatitis virus (MHV) is located at the NTD, most CoVs use the C-domain to bind their receptors. It has been reported that HCoV-OC43 uses 9-O-acetyl-sialic acid (9-O-Ac-Sia) as a receptor, which is terminally linked to oligosaccharides decorating glycoproteins and gangliosides at the host cell surface. HCoV-OC43 appears to bind 9-O-Ac-Sia at the NTD. Due to the key role of the S protein RBD in viral attachment, it is the major target for antibody-mediated neutralization. This model corresponds to the S1 subunit C-domain that serves as the RBD for most CoVs.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 556015081   5 SVLYNSTSFSTFKCYGVSATKLNDLCFSNVYADSFVVKGDDVRQIAPGQTGVIADYNYKLPDDFTGCVLAWN 76
Cdd:cd21485   51 SSLMSFIQADSFTCNNIDAAKIYGMCFSSITIDKFAIPNGRKVDLQLGNLGYLQSFNYRIDTTATSCQLYYN 122

receptor-binding domain of the S1 subunit of the Spike (S) protein from porcine hemagglutinating encephalomyelitis virus; This group contains the receptor-binding domain (RBD) of the S1 subunit of the spike (S) protein from porcine hemagglutinating encephalomyelitis virus (HEV), which is associated with acute outbreaks of wasting and encephalitis in nursing piglets from pig farms. Porcine HEV is related to the zoonotic SARS and MERS betacoronaviruses, which have high fatality rates and pandemic potential. The CoV S protein is an envelope glycoprotein that plays the most important role in viral attachment, fusion, and entry into host cells, and serves as a major target for the development of neutralizing antibodies, inhibitors of viral entry, and vaccines. It is synthesized as a precursor protein that is cleaved into an N-terminal S1 subunit (~700 amino acids) and a C-terminal S2 subunit (~600 amino acids) that mediates attachment and membrane fusion, respectively. Three S1/S2 heterodimers assemble to form a trimer spike protruding from the viral envelope. The S1 subunit contains a receptor-binding domain (RBD), while the S2 subunit contains a hydrophobic fusion peptide and two heptad repeat regions. S1 contains two structurally independent domains, the N-terminal domain (NTD) and the C-terminal domain (C-domain). Depending on the virus, either the NTD or the C-domain can serve as the receptor-binding domain (RBD). While the RBD of mouse hepatitis virus (MHV) is located at the NTD, most CoVs use the C-domain to bind their receptors. The protein receptor for porcine HEV has not yet been identified. Due to the key role of the S protein RBD in viral attachment, it is the major target for antibody-mediated neutralization. This model corresponds to the S1 subunit C-domain that serves as the RBD for most CoVs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556015081  15 TFKCYGVSATKLNDLCFSNVYADSFVVKGDDVRQIAPGQTGVIADYNYKLPDDFTGCVLAWNTRNIDATQTgNYNYKYRS 94
Cdd:cd21508   61 SFGCNNIDASRLYGMCFGSITIDKFAIPNSRKVDLQVGKSGYLQSFNYKIDTAVSSCQLYYSLPAANVSVT-HYNPSSWN 139

                 ....
gi 556015081  95 LRHG 98
Cdd:cd21508  140 RRYG 143

receptor-binding domain of the S1 subunit of the Spike (S) protein from Tylonycteris bat coronavirus HKU4 and similar proteins; This group contains the receptor-binding domain (RBD) of the S1 subunit of the spike (S) protein from Tylonycteris bat coronavirus HKU4 and other Middle East Respiratory Syndrome (MERS)-related coronaviruses. The CoV S protein is an envelope glycoprotein that plays the most important role in viral attachment, fusion, and entry into host cells, and serves as a major target for the development of neutralizing antibodies, inhibitors of viral entry, and vaccines. It is synthesized as a precursor protein that is cleaved into an N-terminal S1 subunit (~700 amino acids) and a C-terminal S2 subunit (~600 amino acids) that mediates attachment and membrane fusion, respectively. Three S1/S2 heterodimers assemble to form a trimer spike protruding from the viral envelope. The S1 subunit contains a receptor-binding domain (RBD), while the S2 subunit contains a hydrophobic fusion peptide and two heptad repeat regions. S1 contains two structurally independent domains, the N-terminal domain (NTD) and the C-terminal domain (C-domain). Depending on the virus, either the NTD or the C-domain can serve as the receptor-binding domain (RBD). While the RBD of mouse hepatitis virus (MHV) is located at the NTD, most CoVs, including human MERS-CoV that is phylogenetically closely related to bat CoV HKU4 use the C-domain to bind their receptors. HKU4 is able to bind the MERS-CoV receptor, human dipeptidyl peptidase 4 (DPP4), also called CD26. Due to the key role of the S protein RBD in viral attachment, it is the major target for antibody-mediated neutralization. This model corresponds to the S1 subunit C-domain that serves as the RBD for most CoVs including MERS-CoV, and most likely, bat CoV HKU4.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 556015081  16 FKCYGVSATKLNDLCFSNVYADSFVVKGDDVRQIAPGQTGVIADYNYKLPDDFTGC-VLAWNTRNIDATQTGNYNY 90
Cdd:cd21487   56 FSCNGISPDAIARGCYSTLTVDYFAYPLSMKSYIRPGSAGNIPLYNYKQSFANPTCrVMASVPANVTITKPEAYGY 131