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Previous and Unofficial Names ![]() |
non-structural protein 12 | nsp12 |
Database Links ![]() |
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ChEMBL Target | CHEMBL5118 (SARS-CoV) |
UniProtKB | P0DTD1 (SARS-CoV-2), P0C6X7 (SARS-CoV) |
Download all structure-activity data for this target as a CSV file
Inhibitors | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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View species-specific inhibitor tables |
General Comments |
Although RdRp is strictly a component of the SARS-CoV-2 replicase polyprotein we have included it as a separate entity to allow us to more sensibly curate pharmacological information (particularly regarding inhibitor development) that is specific for this enzyme. RdRP functions as a component of a genome replication protein complex that also contains nsp7 and nsp8 [2-3]. RdRP-mediated replication can be primer-dependent, but RdRp is also capable of de novo (primer-independent) RNA synthesis. Because of the conserved structure of the key drug-binding pockets between SARS-CoV-2, SARS-CoV, and MERS-CoV RdRPs, repurposing known SARS-CoV and MERS-CoV inhibitors for SARS-CoV-2 is an obvious strategy to combat SARS-CoV-2. To enhance therapeutic efficacy a sensible strategy would be to develop a multi-targeted combination of RdRP inhibitors with approved or clinical-stage drug candidates against other viral and/or host proteins. Although RdRp is strictly a component of the SARS-CoV replicase polyprotein we have included it as a separate entity to allow us to more sensibly curate pharmacological information (particularly regarding inhibitor development) that is specific for this enzyme.RdRP functions as a component of a genome replication protein complex that also contains nsp7 and nsp8 [2-3]. RdRP-mediated replication can be primer-dependent, but RdRp is also capable of de novo (primer-independent) RNA synthesis. It has been suggested that nsp8 is a second, non-canonical RdRP that generates short primers that are used by nsp12 canonical RdRp for primer-dependent RNA synthesis [2]. |
1. Gordon CJ, Tchesnokov EP, Woolner E, Perry JK, Feng JY, Porter DP, Götte M. (2020) Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency. J. Biol. Chem., 295 (20): 6785-6797. [PMID:32284326]
2. Imbert I, Guillemot JC, Bourhis JM, Bussetta C, Coutard B, Egloff MP, Ferron F, Gorbalenya AE, Canard B. (2006) A second, non-canonical RNA-dependent RNA polymerase in SARS coronavirus. EMBO J., 25 (20): 4933-42. [PMID:17024178]
3. Kirchdoerfer RN, Ward AB. (2019) Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors. Nat Commun, 10 (1): 2342. [PMID:31138817]