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Gene and Protein Information  |
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| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Gene and Protein Information Comments | ||||||
| SARS-CoV RdRp is a 932 amino acid protein that is amino acids 4370-5301 of the polyprotein encoded by Orf1b. SARS-CoV-2 RdRp is a 932 amino acid protein that is amino acids 4393-5324 of the polyprotein encoded by Orf1b. |
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| Previous and Unofficial Names |
| non-structural protein 12 | nsp12 |
| Database Links |
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| ChEMBL Target | CHEMBL4523582 (SARS-CoV-2), CHEMBL5118 (SARS-CoV) |
| UniProtKB | P0DTD1 (SARS-CoV-2), P0C6X7 (SARS-CoV) |
| Selected 3D Structures |
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Download all structure-activity data for this target as a CSV file 
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| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| General Comments |
| Coronavirus RdRp is a highly investigated molecular target for antiviral drug development [4,8,12], and is the target of the much publicised drug remdesivir. Although RdRp (nsp12) 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 [5-6]. RdRp-mediated replication can be primer-dependent, but RdRp is also capable of de novo (primer-independent) RNA synthesis [5]. Because of the conserved structure of the key drug-binding pockets between SARS-CoV-2, SARS-CoV, and MERS-CoV RdRps, redeploying 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. |
1. Bolinger AA, Li J, Xie X, Li H, Zhou J. (2024) Lessons learnt from broad-spectrum coronavirus antiviral drug discovery. Expert Opin Drug Discov, 19 (9): 1023-1041. [PMID:39078037]
2. Gao Y, Yan L, Huang Y, Liu F, Zhao Y, Cao L, Wang T, Sun Q, Ming Z, Zhang L et al.. (2020) Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Science, 368 (6492): 779-782. [PMID:32277040]
3. 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]
4. Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O'Meara MJ, Rezelj VV, Guo JZ, Swaney DL et al.. (2020) A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature, 583 (7816): 459-468. [PMID:32353859]
5. 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]
6. 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]
7. Schäfer A, Martinez DR, Won JJ, Moreira FR, Brown AJ, Gully KL, Kalla R, Chun K, Du Pont V, Babusis D et al.. (2021) Therapeutic efficacy of an oral nucleoside analog of remdesivir against SARS-CoV-2 pathogenesis in mice. bioRxiv, Preprint. DOI: 10.1101/2021.09.13.460111 [PMID:34545367]
8. Shahid M, Shahzad-Ul-Hussan S. (2021) Structural insights of key enzymes into therapeutic intervention against SARS-CoV-2. J Struct Biol, 213 (1): 107690. [PMID:33383190]
9. Wei D, Hu T, Zhang Y, Zheng W, Xue H, Shen J, Xie Y, Aisa HA. (2021) Potency and pharmacokinetics of GS-441524 derivatives against SARS-CoV-2. Bioorg Med Chem, 46: 116364. [PMID:34450570]
10. Xie Y, Yin W, Zhang Y, Shang W, Wang Z, Luan X, Tian G, Aisa HA, Xu Y, Xiao G et al.. (2021) Design and development of an oral remdesivir derivative VV116 against SARS-CoV-2. Cell Res, 31 (11): 1212-1214. [PMID:34584244]
11. Yin W, Mao C, Luan X, Shen DD, Shen Q, Su H, Wang X, Zhou F, Zhao W, Gao M et al.. (2020) Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir. Science, 368 (6498): 1499-1504. [PMID:32358203]
12. Zhu W, Chen CZ, Gorshkov K, Xu M, Lo DC, Zheng W. (2020) RNA-Dependent RNA Polymerase as a Target for COVID-19 Drug Discovery. SLAS Discov, 25 (10): 1141-1151. [PMID:32660307]
