Progresses on the SARS-CoV-2 RNA-dependent RNA polymerase and potential anti-SARS-CoV-2 inhibitors

doi:10.3969/j.issn.2096-8493.2020.01.003

Abstract

Abstract:

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerges as global pandemic and public crisis. Due to the lack of specific antiviral therapy and vaccines, it is urgent for novel drugs and vaccines based on the molecular biology of the virus. As a positive single-stranded RNA virus, SARS-CoV-2 replication in host cells depends on its own RNA-dependent RNA polymerase (RdRp). Based on the high conservative of RdRp, this paper summarizes the progress of anti-coronavirus RdRp inhibitors as well as the structure and function of SARS-CoV-2 RdRp, with an aim to find drugs capable of inhibiting the RdRp function of SARS-CoV-2 and treatment of COVID-19.

Key words: Coronavirus disease 2019(COVID-19), Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), RNA replicase, Enzyme inhibitors

LI Gang, XIE Jian-ping. Progresses on the SARS-CoV-2 RNA-dependent RNA polymerase and potential anti-SARS-CoV-2 inhibitors[J]. Journal of Tuberculosis and Lung Disease , 2020, 1(1): 6-10. doi: 10.3969/j.issn.2096-8493.2020.01.003

References 34

[1]	World Health Organization. Novel Coronavirus(2019-nCoV) Situation Report-22. Geneva: World Health Organization, 2020.
[2]	Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol, 2020,5(4):536-544. doi: 10.1038/s41564-020-0695-z. URL pmid: 32123347
[3]	Sheahan TP, Sims AC, Leist SR, et al. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Commun, 2020,11(1):222. doi: 10.1038/s41467-019-13940-6. doi: 10.1038/s41467-019-13940-6 URL pmid: 31924756
[4]	Arabi YM, Asiri AY, Assiri AM, et al. Treatment of Middle East respiratory syndrome with a combination of lopinavir/ritonavir and interferon-beta1b (MIRACLE trial): statistical analysis plan for a recursive two-stage group sequential randomized controlled trial. Trials, 2020,21(1):8. doi: 10.1186/s13063-019-3846-x.
[5]	Arabi YM, Alothman A, Balkhy HH, et al. Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-beta1b (MIRACLE trial): study protocol for a randomized controlled trial. Trials, 2018,19(1):81. doi: 10.1186/s13063-017-2427-0. URL pmid: 29382391
[6]	中华人民共和国国家卫生健康委员会办公厅. 新型冠状病毒肺炎防控方案(第五版). 国卫办疾控函[2020]156号. 2020-02-21.
[7]	Chan JF, Lau SK, To KK, et al. Middle East respiratory syndrome coronavirus: another zoonotic betacoronavirus causing SARS-like disease. Clin Microbiol Rev, 2015,28(2):465-522. doi: 10.1128/CMR.00102-14. doi: 10.1128/CMR.00102-14 URL
[8]	Lange CM, Sarrazin C, Zeuzem S. Review article: specifically targeted anti-viral therapy for hepatitis C-a new era in therapy. Aliment Pharmacol Ther, 2010,32(1):14-28. doi: 10.1111/j.1365-2036.2010.04317.x. doi: 10.1111/j.1365-2036.2010.04317.x URL
[9]	Cleri DJ, Ricketti AJ, Vernaleo JR. Severe acute respiratory syndrome (SARS). Infect Dis Clin North Am, 2010,24(1):175-202. doi: 10.1016/j.idc.2009.10.005. doi: 10.1016/j.idc.2009.10.005 URL
[10]	Arabi YM, Balkhy HH, Hayden FG, et al. Middle East Respiratory Syndrome. N Engl J Med, 2017,376(6):584-594. doi: 10.1056/NEJMsr1408795. doi: 10.1056/NEJMsr1408795 URL pmid: 28177862
[11]	Zumla A, Chan JF, Azhar EI, et al. Coronaviruses-drug discovery and therapeutic options. Nat Rev Drug Discov, 2016,15(5):327-347. doi: 10.1038/nrd.2015.37. doi: 10.1038/nrd.2015.37 URL pmid: 26868298
[12]	Ung COL. Community pharmacist in public health emergencies: Quick to action against the coronavirus 2019-nCoV outbreak. Res Social Adm Pharm, 2020,16(4):583-586. doi: 10.1016/j.sapharm.2020.02.003. doi: 10.1016/j.sapharm.2020.02.003 URL pmid: 32081569
[13]	Ksiazek TG, Erdman D, Goldsmith CS, et al. A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med, 2003,348(20):1953-1966. doi: 10.1056/NEJMoa030781.
[14]	Snijder EJ, Bredenbeek PJ, Dobbe JC, et al. Unique and conserved features of genome and proteome of SARS-coronavirus, an early split-off from the coronavirus group 2 lineage. J Mol Biol, 2003,331(5):991-1004. doi: 10.1016/s0022-2836(03)00865-9. doi: 10.1016/s0022-2836(03)00865-9 URL pmid: 12927536
[15]	Subissi L, Posthuma CC, Collet A, et al. One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities. Proc Natl Acad Sci U S A, 2014,111(37):E3900-3909. doi: 10.1073/pnas.1323705111. doi: 10.1073/pnas.1323705111 URL pmid: 25197083
[16]	Goldsmith CS, Tatti KM, Ksiazek TG, et al. Ultrastructural characterization of SARS coronavirus. Emerg Infect Dis, 2004,10(2):320-326. doi: 10.3201/eid1002.030913. doi: 10.3201/eid1002.030913 URL pmid: 15030705
[17]	Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 2020,395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. doi: 10.1016/S0140-6736(20)30183-5 URL pmid: 31986264
[18]	Chan PK, Chan MC. Tracing the SARS-coronavirus. J Thorac Dis, 2013,5 Suppl 2: S118-121. doi: 10.3978/j.issn.2072-1439.2013.06.19.
[19]	Ziebuhr J. The coronavirus replicase. Curr Top Microbiol Immunol, 2005,287:57-94. doi: 10.1007/3-540-26765-4_3. doi: 10.1007/3-540-26765-4_3 URL pmid: 15609509
[20]	Gao Y, Yan L, Huang Y, et al. Structure of RNA-dependent RNA polymerase from 2019-nCoV, a major antiviral drug target[J/OL]. bioRxiv, 2020 [2020-04-01]. doi: 10.1101/2020.03.16.993386.
[21]	Lehmann KC, Gulyaeva A, Zevenhoven Dobbe JC, et al. Discovery of an essential nucleotidylating activity associated with a newly delineated conserved domain in the RNA polymerase-containing protein of all nidoviruses. Nucleic Acids Res, 2015,43(17):8416-8434. doi: 10.1093/nar/gkv838. doi: 10.1093/nar/gkv838 URL pmid: 26304538
[22]	Appleby TC, Perry JK, Murakami E, et al. Viral replication. Structural basis for RNA replication by the hepatitis C virus polymerase. Science, 2015,347(6223):771-775. doi: 10.1126/science.1259210. doi: 10.1126/science.1259210 URL pmid: 25678663
[23]	Steinhauer DA, Domingo E, Holland JJ. Lack of evidence for proofreading mechanisms associated with an RNA virus polymerase. Gene, 1992,122(2):281-288. doi: 10.1016/0378-1119(92)90216-c. doi: 10.1016/0378-1119(92)90216-c URL pmid: 1336756
[24]	Eckerle LD, Becker MM, Halpin RA, et al. Infidelity of SARS-CoV Nsp14-exonuclease mutant virus replication is revealed by complete genome sequencing. PLoS Pathog, 2010,6(5):e1000896. doi: 10.1371/journal.ppat.1000896. doi: 10.1371/journal.ppat.1000896 URL pmid: 20463816
[25]	Eckerle LD, Lu X, Sperry SM, et al. High fidelity of murine hepatitis virus replication is decreased in nsp14 exoribonuclease mutants. J Virol, 2007,81(22):12135-12144. doi: 10.1128/JVI.01296-07. doi: 10.1128/JVI.01296-07 URL pmid: 17804504
[26]	Smith EC, Blanc H, Surdel MC, et al. Coronaviruses lacking exoribonuclease activity are susceptible to lethal mutagenesis: evidence for proofreading and potential therapeutics. PLoS Pathog, 2013,9(8):e1003565. doi: 10.1371/journal.ppat.1003565. doi: 10.1371/journal.ppat.1003565 URL pmid: 23966862
[27]	Graham RL, Donaldson EF, Baric RS. A decade after SARS: strategies for controlling emerging coronaviruses. Nat Rev Microbiol, 2013,11(12):836-848. doi: 10.1038/nrmicro3143. doi: 10.1038/nrmicro3143 URL pmid: 24217413
[28]	Du L, He Y, Zhou Y, et al. The spike protein of SARS-CoV—a target for vaccine and therapeutic development. Nat Rev Microbiol, 2009,7(3):226-236. doi: 10.1038/nrmicro2090. doi: 10.1038/nrmicro2090 URL pmid: 19198616
[29]	Pillaiyar T, Manickam M, Namasivayam V, et al. An Overview of Severe Acute Respiratory Syndrome-Coronavirus (SARS-CoV) 3CL Protease Inhibitors: Peptidomimetics and Small Molecule Chemotherapy. J Med Chem, 2016,59(14):6595-6628. doi: 10.1021/acs.jmedchem.5b01461. doi: 10.1021/acs.jmedchem.5b01461 URL pmid: 26878082
[30]	Delang L, Abdelnabi R, Neyts J. Favipiravir as a potential countermeasure against neglected and emerging RNA viruses. Antiviral Res, 2018,153:85-94. doi: 10.1016/j.antiviral.2018.03.00. doi: 10.1016/j.antiviral.2018.03.003 URL pmid: 29524445
[31]	Delang L, Segura Guerrero N, Tas A, et al. Mutations in the chikungunya virus non-structural proteins cause resistance to favipiravir (T-705), a broad-spectrum antiviral. J Antimicrob Chemother, 2014,69(10):2770-2784. doi: 10.1093/jac/dku209. doi: 10.1093/jac/dku209 URL pmid: 24951535
[32]	Olschlager S, Neyts J, Gunther S. Depletion of GTP pool is not the predominant mechanism by which ribavirin exerts its antiviral effect on Lassa virus. Antiviral Res, 2011,91(2):89-93. doi: 10.1016/j.antiviral.2011.05.006. doi: 10.1016/j.antiviral.2011.05.006 URL pmid: 21616094
[33]	Holshue ML, DeBolt C, Lindquist S, et al. First Case of 2019 Novel Coronavirus in the United States. N Engl J Med, 2020,382(10):929-936. doi: 10.1056/NEJMoa2001191. doi: 10.1056/NEJMoa2001191 URL pmid: 32004427
[34]	Cheng VC, Chan JF, To KK, et al. Clinical management and infection control of SARS: lessons learned. Antiviral Res, 2013,100(2):407-419. doi: 10.1016/j.antiviral.2013.08.016. doi: 10.1016/j.antiviral.2013.08.016 URL pmid: 23994190