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 2065947492   1 MPSMIRMLAAMVLGSKHVTCCTDSDRFYRLSNELAQVLNEVVHSNGGFYVKPGGTTSGDATTAYANSVFNIFQAVSSNIN 80
Cdd:cd21588   618 LPNMIRMISAMILGSKHVTCCTHSDRFYRLCNELAQVLTEVVYSNGGFYLKPGGTTSGDATTAYANSVFNIFQAVSANVN 697

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 2065947492  81 RLLSVDSNVCNNLYVKKLQRSIYDNCYRSSAVDDNVVTDFYNYLKKHFS 129
Cdd:cd21588   698 RLLSVDSNTCNNLTVKSLQRKLYDNCYRSSSVDDSFVDEYYGYLRKHFS 746

alphacoronavirus 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 alphacoronaviruses, including human coronaviruses (HCoVs), HCoV-NL63, and HCoV-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. 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        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2065947492   1 MPSMIRMLAAMVLGSKHVTCCTDSDRFYRLSNELAQVLNEVVHSNGGFYVKPGGTTSGDATTAYANSVFNIFQAVSSNIN 80
Cdd:cd21588   618 LPNMIRMISAMILGSKHVTCCTHSDRFYRLCNELAQVLTEVVYSNGGFYLKPGGTTSGDATTAYANSVFNIFQAVSANVN 697

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 2065947492  81 RLLSVDSNVCNNLYVKKLQRSIYDNCYRSSAVDDNVVTDFYNYLKKHFS 129
Cdd:cd21588   698 RLLSVDSNTCNNLTVKSLQRKLYDNCYRSSSVDDSFVDEYYGYLRKHFS 746

alphacoronavirus 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 alphacoronaviruses, including human coronaviruses (HCoVs), HCoV-NL63, and HCoV-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. 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        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2065947492   1 MPSMIRMLAAMVLGSKHVTCCTDSDRFYRLSNELAQVLNEVVHSNGGFYVKPGGTTSGDATTAYANSVFNIFQAVSSNIN 80
Cdd:cd21588   618 LPNMIRMISAMILGSKHVTCCTHSDRFYRLCNELAQVLTEVVYSNGGFYLKPGGTTSGDATTAYANSVFNIFQAVSANVN 697

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 2065947492  81 RLLSVDSNVCNNLYVKKLQRSIYDNCYRSSAVDDNVVTDFYNYLKKHFS 129
Cdd:cd21588   698 RLLSVDSNTCNNLTVKSLQRKLYDNCYRSSSVDDSFVDEYYGYLRKHFS 746

Bat coronavirus HKU9 RNA-dependent RNA polymerase, also known as non-structural protein 12, and similar proteins from betacoronaviruses in the D lineage: responsible for replication and transcription of the viral RNA genome; This group contains the RNA-dependent RNA polymerase (RdRp) of bat coronavirus HKU9 and similar proteins from betacoronaviruses in the nobecovirus subgenera (D 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        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2065947492   1 MPSMIRMLAAMVLGSKHVTCCTDSDRFYRLSNELAQVLNEVVHSNGGFYVKPGGTTSGDATTAYANSVFNIFQAVSSNIN 80
Cdd:cd21596   623 MPNLLRIFASLILARKHSTCCNASERFYRLANECAQVLSEMVLCGGGFYVKPGGTSSGDSTTAYANSVFNICQAVSANLN 702

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 2065947492  81 RLLSVDSNVCNNLYVKKLQRSIYDNCYRSSAVDDNVVTDFYNYLKKHFS 129
Cdd:cd21596   703 TFLSIDGNKIYTTYVQELQRRLYLGIYRSNTVDNELVLDYYNYLRKHFS 751

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        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2065947492   1 MPSMIRMLAAMVLGSKHVTCCTDSDRFYRLSNELAQVLNEVVHSNGGFYVKPGGTTSGDATTAYANSVFNIFQAVSSNIN 80
Cdd:cd21593   619 MPNILRIVSSLVLARKHDSCCSHGDRFYRLANECAQVLSEIVMCGGCYYVKPGGTSSGDATTAFANSVFNICQAVSANVC 698

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 2065947492  81 RLLSVDSNVCNNLYVKKLQRSIYDNCYRSSAVDDNVVTDFYNYLKKHFS 129
Cdd:cd21593   699 SLMACNGHKIEDLSIRELQKRLYSNVYRSDYVDPTFVNEYYEFLNKHFS 747

Severe acute respiratory syndrome coronavirus RNA-dependent RNA polymerase, also known as non-structural protein 12, and similar proteins from betacoronaviruses in the B lineage: responsible for replication and transcription of the viral RNA genome; This group contains the RNA-dependent RNA polymerase (RdRp) of Severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2 (also known as 2019 novel CoV (2019-nCoV) or COVID-19 virus), and similar proteins from betacoronaviruses in the sarbecovirus subgenera (B 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 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. Recent studies have shown that the SARS-CoV-2 RdRp requires two iron-sulfur clusters to function optimally. Earlier studies had mistakenly identified these iron-sulfur cluster binding sites for zinc-binding sites, likely because iron-sulfur clusters degrade easily under standard experimental conditions.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 2065947492   1 MPSMIRMLAAMVLGSKHVTCCTDSDRFYRLSNELAQVLNEVVHSNGGFYVKPGGTTSGDATTAYANSVFNIFQAVSSNIN 80
Cdd:cd21591   622 MPNMLRIMASLVLARKHTTCCSLSHRFYRLANECAQVLSEMVMCGGSLYVKPGGTSSGDATTAYANSVFNICQAVTANVN 701

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 2065947492  81 RLLSVDSNVCNNLYVKKLQRSIYDNCYRSSAVDDNVVTDFYNYLKKHFS 129
Cdd:cd21591   702 ALLSTDGNKIADKYVRNLQHRLYECLYRNRDVDTDFVNEFYAYLRKHFS 750

deltacoronavirus 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 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. 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 inhibit human endemic and zoonotic deltacoronaviruses with a highly divergent 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        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2065947492   1 MPSMIRMLAAMVLGSKHvTCCTDSDRFYRLSNELAQVLNEVVHSNGGFYVKPGGTTSGDATTAYANSVFNIFQAVSSNIN 80
Cdd:cd21590   624 MPNMLRIAASCLLARKH-TCCNQSQRFYRLANECCQVLSEVVVSGNNLYVKPGGTSSGDATTAYANSVFNILQVVSANVA 702

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 2065947492  81 RLLSVDSNVCNNLYVKKLQRSIYDNCYRSSAVDDNVVTDFYNYLKKHF 128
Cdd:cd21590   703 TFLSTSTTSHINKDIADLHRSLYEDIYRGDSNDITVINRFYQHLQSYF 750

catalytic core domain of RNA-dependent RNA polymerase (RdRP) in the Tobaniviridae family of positive-sense single-stranded RNA [(+)ssRNA] viruses; This group contains the catalytic core domain of RdRp of RNA viruses belonging to the family Tobaniviridae, order Nidovirales. Tobaniviridae RNA viruses infect vertebrates; their host organisms include mammals, fish, and snakes. Member viruses have a viral envelope and (+)ssRNA genome. The genome size of Tobaniviruses ranges from 20 to 32 kilobases. The family is the only member of the suborder Tornidovirineae. The family Tobaniviridae has four subfamilies (Piscanivirinae, Remotovirinae, Remotovirinae, and Torovirinae) and eight genera (Bafinivirus, Oncotshavirus, Bostovirus, Infratovirus, Pregotovirus, Sectovirus, Tiruvirus, and Torovirus). The Tobaniviridae family belongs to the order Nidovirales, which currently comprises 88 formally recognized virus species of (+)ssRNA viruses, which are classified into nine virus families across seven different suborders. The structure of Tobaniviridae RdRp 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        40
                  ....*....|....*....|....*....|....*....|.
gi 2065947492  32 NELAQVLNEVVHSNGGFYVKPGGTTSGDATTAYANSVFNIF 72
Cdd:cd23186   201 NEIFAFMLDFVFIGGHIFNKPGGTSSGDATTAFSNTLYNYM 241

catalytic core domain of RNA-dependent RNA polymerase (RdRp) in the family Arteriviridae of positive-sense single-stranded RNA [(+)ssRNA] viruses; This group contains the catalytic core domain of RdRp of RNA viruses belonging to the family Arteriviridae, order Nidovirales. Member viruses have a viral envelope and (+)ssRNA genome. The overall genome organization of the Arteriviruses are highly similar to the Coronaviruses; however, they lack the spike proteins of the coronaviruses. The family members include equine arteritis virus (EAV), porcine reproductive and respiratory syndrome virus (PRRSV), lactate dehydrogenase elevating virus of mice, and simian hemorrhagic fever virus (SHFV). The structure of Arteriviridae RdRp 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        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2065947492   2 PSMIRMLAAMVLGSKhvTCCTDSDRFYrlsnelaqVLN---EVVHSNGGFYVKPGGTTSGDATTAYANSVF 69
Cdd:cd23189    88 PAIVRWFAANLLFEL--ACAEECLPSY--------VLNcchDLLVTQSGAFTKRGGLSSGDPVTSISNTIY 148