SII-SWORD/CoKE huggingface dataset:
Non-structural protein 3c, bat coronavirus HKU5 (ORF4b_HKU5-CoV)
Type: Family

This entry represents the accessory protein 4b, ORF4b (also called NS3c protein) of Pipistrellus bat coronavirus HKU5 and related proteins from bat coronaviruses.

ORF4b/NS3c plays a role in the inhibition of host innate immunity by inhibiting the interaction between host IkappaB kinase epsilon (IKBKE or IKKE) and mitochondrial antiviral-signalling protein (MAVS). In turn, this inhibition prevents the production of host interferon beta. Additionally, it may also interfere with host antiviral response within the nucleus. ORF4b/NS3c proteins in this subgroup are similar to the MERS-CoV ORF4b (also known as MERS-CoV 4b) which has been shown to interfere with the NF-kappaB-dependent innate immune response during infection, as well as antagonizing the early antiviral alpha/beta interferon (IFN-alpha/beta) response, which may significantly contribute to MERS-CoV pathogenesis .
Non-structural protein 3c (NS3c), bat coronavirus HKU4-like (ORF4b_HKU4-CoV)
Type: Family

This entry represents the accessory protein 4b, ORF4b (also called NS3c protein) of Tylonycteris bat coronavirus HKU4 and related bat coronaviruses including Tylonycteris pachypus bat coronavirus HKU4-related.

ORF4b/NS3c plays a role in the inhibition of host innate immunity by inhibiting the interaction between host IkappaB kinase epsilon (IKBKE or IKKE) and mitochondrial antiviral-signalling protein (MAVS). In turn, this inhibition prevents the production of host interferon beta. Additionally, it may also interfere with host antiviral response within the nucleus. ORF4b/NS3c proteins in this subgroup are similar to the MERS-CoV ORF4b (also known as MERS-CoV 4b) which has been shown to interfere with the NF-kappaB-dependent innate immune response during infection, as well as antagonizing the early antiviral alpha/beta interferon (IFN-alpha/beta) response, which may significantly contribute to MERS-CoV pathogenesis .
NSP11, N-terminal, arterivirus (NSP11_Av_N)
Type: Domain

This entry represents the N-terminal domain of Nsp11 from arteriviruses.

Nidovirus endoribonucleases (NendoUs) are uridylate-specific endoribonucleases, which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. They are conserved among this order and a genetic marker of nidoviruses . A feature of these viruses' evolutionary relationship is the organisation and processing of the genome, which is translated in two large precursor polyproteins (pp1a and pp1ab) from the replicase gene, that are proteolytically processed by virus proteases into 13 to 16 nonstructural proteins (NSPs) .

Proteins containing the NendoU domain include NSP15 from coronaviruses and NSP11 from arteriviruses, both of which participate in the viral replication process and in the evasion of the host immune system. Although they are similar and conserved, they only share 27% identical residues and show structural differences . NSP11 has an N-terminal domain and a C-terminal NendoU catalytic domain. NSP11 functions as a dimer and Mg2 is dispensable for its activity. In Porcine reproductive and respiratory syndrome virus (PRRSV), NSP11 induces STAT2 degradation to inhibit interferon signaling. Mutagenesis studies revealed that the amino acid residue K59 located at the N-terminal domain of NSP11 is indispensable for inducing STAT2 reduction . This domain is not conserved in those nidovirus branches that replicate in invertebrate hosts (Mesoniviridae, Roniviridae), suggesting specific roles in vertebrate hosts.
Non-structural protein 3c (NS3c), Middle East respiratory syndrome (MERS)-related CoV (ORF4b_MERS-CoV-like)
Type: Family

This entry represents the accessory protein 4b, ORF4b (also called NS3c protein) of Middle East respiratory syndrome (MERS)-related CoV, as well as some bat coronaviruses.

ORF4b/NS3c plays a role in the inhibition of host innate immunity by inhibiting the interaction between host IkappaB kinase epsilon (IKBKE or IKKE) and mitochondrial antiviral-signalling protein (MAVS). In turn, this inhibition prevents the production of host interferon beta. Additionally, it may also interfere with host antiviral response within the nucleus. ORF4b/NS3c proteins in this subgroup are similar to the MERS-CoV ORF4b (also known as MERS-CoV 4b) which has been shown to interfere with the NF-kappaB-dependent innate immune response during infection, as well as antagonizing the early antiviral alpha/beta interferon (IFN-alpha/beta) response, which may significantly contribute to MERS-CoV pathogenesis .
Nonstructural protein 15, middle domain, alpha/betacoronavirus (NSP15_M_alpha_beta_CoV)
Type: Domain

The unique coronavirus transcription/replication machinery comprised of multiple virus-encoded non structural proteins (NSP) plays a vital role during initial and intermediate phases of the viral life cycle. NSP15 forms a hexamer made of dimers of trimers which is suggested to be a functional unit, responsible for the endoribonuclease activity. The NSP15 monomer consists of three domains: N-terminal, middle and C-terminal . The catalytic function of NSP15 resides in the C-terminal NendoU domain. The active site carries six key residues conserved among SARS-CoV-2, SARS-CoV and MERS-CoV, suggesting that its activity is important for sustained replication in the host .

This entry represents the non-catalytic middle domain of NSP15 from alpha and beta coronaviruses. This domain is formed by ten β-strands organised into three β-hairpins. It creates concave surfaces that may serve as interaction hubs with other proteins and RNA . Coronavirus Nsp15 from Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), human Coronavirus 229E (HCoV229E), and Murine Hepatitis Virus (MHV) form a functional hexamer. This middle domain harbours residues involved in hexamer formation and in trimer stability . Oligomerization of Porcine DeltaCoronavirus (PDCoV) Nsp15 differs from that of the other coronaviruses; it has been shown to exist as a dimer and a monomer in solution .
Non-structural protein ORF5, MERS-CoV-like (MERS-CoV-like_ORF5)
Type: Family

This entry represents the non-structural protein ORF5 from Middle East respiratory syndrome-related coronavirus (MERS-CoV) and similar proteins from betacoronaviruses in the merbecovirus subgenera (C lineage). ORF5 is also called non-structural protein 3d (NS3d) or accessory protein 3d in some bat merbecoviruses. MERS-CoV is a highly pathogenic respiratory virus with pathogenic mechanisms that may be driven by innate immune pathways. MERS-CoV ORF5 acts as an interferon antagonist and may play a role in circumventing the innate immunity of host cells . ORF5/NS3d from merbecovirus (betacoronavirus, lineage C) may not be related to ORF5 proteins from other lineages.
Nonstructural protein 15, middle domain, deltacoronavirus (NSP15_M_deltaCoV)
Type: Domain

The unique coronavirus transcription/replication machinery comprised of multiple virus-encoded non structural proteins (NSP) plays a vital role during initial and intermediate phases of the viral life cycle. NSP15 forms a hexamer made of dimers of trimers which is suggested to be a functional unit, responsible for the endoribonuclease activity. The NSP15 monomer consists of three domains: N-terminal, middle and C-terminal . The catalytic function of NSP15 resides in the C-terminal NendoU domain. The active site carries six key residues conserved among SARS-CoV-2, SARS-CoV and MERS-CoV, suggesting that its activity is important for sustained replication in the host .

This entry represents the middle domain of NSP15 from deltacoronaviruses. This domain is formed by ten β strands organised into three β hairpins. It creates concave surfaces that may serve as interaction hubs with other proteins and RNA . Coronavirus Nsp15 from Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), human Coronavirus 229E (HCoV229E), and Murine Hepatitis Virus (MHV) form a functional hexamer. This middle domain harbours residues involved in hexamer formation and in trimer stability . Oligomerization of Porcine DeltaCoronavirus (PDCoV) Nsp15 differs from that of the other coronaviruses; it has been shown to exist as a dimer and a monomer in solution and that it inhibits type I interferon production independently of its endoribonuclease activity .
Nonstructural protein 15, middle domain, gammacoronavirus (NSP15_M_gammaCoV)
Type: Domain

The unique coronavirus transcription/replication machinery comprised of multiple virus-encoded non structural proteins (NSP) plays a vital role during initial and intermediate phases of the viral life cycle. NSP15 forms a hexamer made of dimers of trimers which is suggested to be a functional unit, responsible for the endoribonuclease activity. The NSP15 monomer consists of three domains: N-terminal, middle and C-terminal . The catalytic function of NSP15 resides in the C-terminal NendoU domain. The active site carries six key residues conserved among SARS-CoV-2, SARS-CoV and MERS-CoV, suggesting that its activity is important for sustained replication in the host .

This entry represents the non-catalytic middle domain of NSP15 from gammacoronaviruses. This domain is formed by ten β strands organised into three β hairpins. It creates concave surfaces that may serve as interaction hubs with other proteins and RNA . Coronavirus Nsp15 from Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), human Coronavirus 229E (HCoV229E), and Murine Hepatitis Virus (MHV) form a functional hexamer. This middle domain harbours residues involved in hexamer formation and in trimer stability . Oligomerization of Porcine DeltaCoronavirus (PDCoV) Nsp15 differs from that of the other coronaviruses; it has been shown to exist as a dimer and a monomer in solution and that it inhibits type I interferon production independently of its endoribonuclease activity .
NS7b protein, bat coronavirus HKU9-like (NS7b_batCoV-HKU9)
Type: Domain

This entry represents the NS7b protein of Rousettus bat coronavirus (CoV) HKU9 and related proteins from betacoronaviruses in the nobecovirus subgenera (D lineage). The NS7b protein of lineage D betacoronavirus is an accessory protein whose function is unknown . It is not related to NS7b proteins from other betacoronavirus lineages.
Nonstructural protein 15, N-terminal, gammacoronavirus (NSP15_gammaCoV_N)
Type: Domain

The unique coronavirus transcription/replication machinery comprised of multiple virus-encoded non structural proteins (NSP) plays a vital role during initial and intermediate phases of the viral life cycle. NSP15 forms a hexamer made of dimers of trimers which is suggested to be a functional unit, responsible for the endoribonuclease activity. The NSP15 monomer consists of three domains: N-terminal, middle and C-terminal . The catalytic function of NSP15 resides in the C-terminal NendoU domain. The active site carries six key residues conserved among SARS-CoV-2, SARS-CoV and MERS-CoV, suggesting that its activity is important for sustained replication in the host .

This entry represents the N-terminal oligomerization domain of the NSP15 from gammacoronaviruses. This domain stabilises the hexamer and is critical for its formation . It is composed of three-stranded antiparallel -βsheet and two α-helices .
Nonstructural protein 15, N-terminal domain, alpha/beta-coronavirus (NSP15_alpha_betaCoV_N)
Type: Domain

The unique coronavirus transcription/replication machinery comprised of multiple virus-encoded non structural proteins (NSP) plays a vital role during initial and intermediate phases of the viral life cycle. NSP15 forms a hexamer made of dimers of trimers which is suggested to be a functional unit, responsible for the endoribonuclease activity. The NSP15 monomer consists of three domains: N-terminal, middle and C-terminal . The catalytic function of NSP15 resides in the C-terminal NendoU domain. The active site carries six key residues conserved among SARS-CoV-2, SARS-CoV and MERS-CoV, suggesting that its activity is important for sustained replication in the host .

This entry represents the N-terminal oligomerization domain of the NSP15, which stabilises the hexamer and is critical for its formation . This domain is composed of three-stranded antiparallel β-sheet and two α-helices .

This entry represents the N-terminal oligomerisation domain of the NSP15 from alpha and beta coronaviruses.
Nonstructural protein 15, N-terminal, deltacoronavirus (NSP15_N_deltaCoV)
Type: Domain

The unique coronavirus transcription/replication machinery comprised of multiple virus-encoded non structural proteins (NSP) plays a vital role during initial and intermediate phases of the viral life cycle. NSP15 forms a hexamer made of dimers of trimers which is suggested to be a functional unit, responsible for the endoribonuclease activity. The NSP15 monomer consists of three domains: N-terminal, middle and C-terminal . The catalytic function of NSP15 resides in the C-terminal NendoU domain. The active site carries six key residues conserved among SARS-CoV-2, SARS-CoV and MERS-CoV, suggesting that its activity is important for sustained replication in the host .

This entry represents the N-terminal oligomerization domain of NSP15 from deltacoronaviruses. This domain stabilises the hexamer and is critical for its formation . It is composed of three-stranded antiparallel β-sheet and two α-helices . In Porcine deltacoronavirus (PDCoV), the N-terminal domain seems to differ from the NSP15 of alpha and betacoronavirus. PDCoV NSP15 has been shown to exist as a dimer and a monomer in solution and that it inhibits type I interferon production independently of its endoribonuclease activity .
Accessory protein NS7a, deltacoronavirus, HKU30-like (NS7a_deltaCoV_HKU30-like)
Type: Domain

This entry includes the accessory protein NS7a from Quail deltacoronavirus (QdCoV) UAE-HKU30 and sparrow deltacoronavirus (SpCoV-HKU17) within the Buldecovirus subgenus of deltacoronaviruses. In deltaCoVs, several avian species encode accessory protein NS7a, which is homologous to Porcine coronavirus (PDCoV) HKU15 accessory proteins NS7 and NS7a. PDCoV NS7a is a 100 amino-acid polypeptide identical to the C-terminal of NS7; it remains unclear whether their functions are redundant. The PDCoV NS7 protein is extensively distributed in the mitochondria and may be involved in various cellular processes such as cytoskeleton networks and cell communication, metabolism, and protein biosynthesis. NS7a proteins in this subfamily have yet to be characterised. Phylogenetic analysis revealed that QdCoV UAE-HKU30 belongs to the same CoV species as porcine deltacoronavirus (PdCoV) HKU15 and sparrow deltacoronavirus (SpdCoV) HKU17 within Buldecovirus subgenus, suggesting transmission between avian and swine hosts .
Accessory protein NS7a, deltacoronavirus, avian coronavirus HKU16-like (NS7a_deltaCoV_HKU16-like)
Type: Domain

This entry includes the accessory protein NS7a from White-eye coronavirus HKU16, Falcon coronavirus UAE-HKU27, Houbara coronavirus UAE-HKU28 and Pigeon coronavirus UAE-HKU29, within the Buldecovirus subgenus of deltacoronaviruses (deltaCoVs). NS7a proteins in this subfamily have yet to be characterised.

In deltaCoVs, several avian species encode accessory protein NS7a, which is homologous to Porcine coronavirus (PDCoV) HKU15 accessory proteins NS7 and NS7a. PDCoV NS7a is a 100 amino-acid polypeptide identical to the C-terminal of NS7; it remains unclear whether their functions are redundant. The PDCoV NS7 protein is extensively distributed in the mitochondria and may be involved in various cellular processes such as cytoskeleton networks and cell communication, metabolism, and protein biosynthesis .
Accessory protein NS7, porcine deltacoronavirus (PDCoV) (NS7_PDCoV)
Type: Domain

This entry includes the accessory protein NS7 found in Porcine coronavirus HKU15. Porcine deltacoronavirus (PDCoV) encodes three accessory proteins, NS6, NS7 and NS7a. NS7a is a 100 amino-acid polypeptide identical to the C-terminal of NS7; it remains unclear whether their functions are redundant . PDCoV HKU15, an emerging swine enteric coronavirus that causes diarrhea in neonatal piglets, has also been found in the respiratory tract of pigs and may be able to cause respiratory infections, thus possibly spreading through the respiratory route . NS7-specific mAbs that recognised cells transfected with an NS7 expression construct or infected with PDCoV also recognized NS7a, which is encoded by a separate subgenome mRNA with a non-canonical transcription regulatory sequence . The NS7 protein is extensively distributed in the mitochondria and may be involved in various cellular processes such as cytoskeleton networks and cell communication, metabolism, and protein biosynthesis. NS7-expressing and PDCoV-infected cells also show a substantial down-regulation of alpha-actinin-4 .
Accessory protein NS6, deltacoronavirus (NS6_deltaCoV)
Type: Domain

This family includes the accessory protein NS6 from deltacoronaviruses such as porcine coronavirus HKU15, and several avian coronaviruses found in sparrow, pigeon, quail and falcon, among others.

Porcine deltacoronavirus (PDCoV) encodes three accessory proteins, NS6, NS7, and NS7a. During PDCoV infection, NS6 antagonizes RIG-I-like receptor (RLR)-mediated IFN-beta production to evade host innate immune defense; it interacts with RIG-I and MDA5 to impede their association with double-stranded RNA. This is an important finding towards novel therapeutic targets and may lead to the development of more effective vaccines against PDCoV infection .
SF1 helicase, zinc-binding domain, tornidovirus (SF1_Hel_ZBD_tv)
Type: Domain

This entry represents the Cys/His rich zinc-binding domain (ZBD) of SF1 helicase from tornidovirus which includes White bream virus (WBV). This domain has 3 zinc-finger motifs . This group of viruses belong to Nidovirales order and it shares the same genome organisation. It encodes the large polyprotein pp1a which is then proteolytically processed to produce the enzymes required for the replicative machinery. This is a novel cluster of nidoviruses that significantly diverged from toroviruses and, even more, from coronaviruses, roniviruses, and arteriviruses .
Spike (S) protein S1 subunit, N-terminal domain, MERS-CoV-like (Spike_S1_N_MERS-CoV-like)
Type: Domain

The CoV Spike (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 synthesised 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). Most CoVs, including SARS-CoV-2, SARS-CoV, and MERS-CoV use the C-domain to bind their receptors. However, CoV such as mouse hepatitis virus (MHV) uses the NTD to bind its receptor, mouse carcinoembryonic antigen related cell adhesion molecule 1a (mCEACAM1a). The S1 NTD contributes to the Spike trimer interface .

This entry represents the N-terminal domain (NTD) of the S1 subunit of the Spike (S) proteins from betacoronaviruses in the merbecovirus subgenera (C lineage), including Middle East respiratory syndrome (MERS) CoV and related bat CoVs.
Spike (S) protein S1 subunit, N-terminal domain, HKU9-like (Spike_S1_N_batCoV-HKU9-like)
Type: Domain

This entry contains the N-terminal domain (NTD) of the S1 subunit of the Spike (S) proteins from betacoronaviruses in the nobecovirus subgenera (D lineage), including Rousettus bat coronavirus HKU9 and related bat CoVs.

The CoV Spike (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 synthesised 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). Most CoVs, including SARS-CoV-2, SARS-CoV, and MERS-CoV use the C-domain to bind their receptors. However, CoV such as mouse hepatitis virus (MHV) uses the NTD to bind its receptor, mouse carcinoembryonic antigen related cell adhesion molecule 1a (mCEACAM1a). The S1 NTD contributes to the Spike trimer interface .
Spike (S) protein S1 subunit, N-terminal domain, murine hepatitis virus-like (Spike_S1_NTD_MHV-like)
Type: Domain

The CoV Spike (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 synthesised 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). Most CoVs, including SARS-CoV-2, SARS-CoV, and MERS-CoV use the C-domain to bind their receptors. However, CoV such as mouse hepatitis virus (MHV) uses the NTD to bind its receptor, mouse carcinoembryonic antigen related cell adhesion molecule 1a (mCEACAM1a). The S1 NTD contributes to the Spike trimer interface .

This entry represents the N-terminal domain (NTD) of the S1 subunit of the Spike (S) proteins from betacoronaviruses in the embecovirus subgenera (A lineage), including murine hepatitis virus (MHV), human coronavirus (HCoV) HKU1 and OC43, and bovine CoV (BCoV). MHV is the most common viral pathogen in contemporary laboratory mouse colonies manifesting as a primary infection in the upper respiratory tract, while HCoV-HKU1 causes mild yet prevalent respiratory disease in humans .
Helicase Sen1, 1B domain (Helicase_Sen1_1B_dom)
Type: Domain

The yeast helicase Sen1 is an ATP-dependent 5'->3' DNA/RNA helicase required for the expression and maturation of diverse classes of non-protein-coding RNAs like precursor tRNAs, rRNAs and small nuclear (snRNA) and nucleolar (snoRNA) RNAs and it also has an ATPase-dependent ability of promoting transcription termination in vitro . Sen1 has a key role at replication forks during DNA replication to promote fork progression and chromosome stability . Sen1 belongs to the superfamily 1B UPF1-like family of helicases with a common domain organisation: a N-terminal domain and a C-terminal domain which contains the SF1B helicase with two RecA domains (RecA1 and RecA2) and the classical helicase motifs involved in nucleic acid binding and ATP hydrolysis. It also contains two SF1B-specific subdomains (1B and 1C) that modulate RNA binding. This entry represents the 1B regulatory domain found in the helicase Sen1 from S. cerevisiae, which has a more elaborate topology of the 1B barrel domain from that of UPF1 .