气候变化领域集成服务门户(CCPortal): Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir

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DOI	10.1126/science.abc1560
	Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir
	Yin W.; Mao C.; Luan X.; Shen D.-D.; Shen Q.; Su H.; Wang X.; Zhou F.; Zhao W.; Gao M.; Chang S.; Xie Y.-C.; Tian G.; Jiang H.-W.; Tao S.-C.; Shen J.; Jiang Y.; Jiang H.; Xu Y.; Zhang S.; Zhang Y.; Xu H.E.
发表日期	2020
ISSN	10959203
起始页码	1499
结束页码	1504
卷号	368 期号:6498
英文摘要	The pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global crisis. Replication of SARS-CoV-2 requires the viral RNA-dependent RNA polymerase (RdRp) enzyme, a target of the antiviral drug remdesivir. Here we report the cryo-electron microscopy structure of the SARS-CoV-2 RdRp, both in the apo form at 2.8-angstrom resolution and in complex with a 50-base template-primer RNA and remdesivir at 2.5-angstrom resolution. The complex structure reveals that the partial double-stranded RNA template is inserted into the central channel of the RdRp, where remdesivir is covalently incorporated into the primer strand at the first replicated base pair, and terminates chain elongation. Our structures provide insights into the mechanism of viral RNA replication and a rational template for drug design to combat the viral infection. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
关键词	adenosine phosphate alanine antivirus agent enzyme inhibitor multiprotein complex NSP7 protein, SARS-CoV-2 NSP8 protein, SARS-CoV-2 remdesivir RNA directed RNA polymerase RNA-dependent RNA polymerase, coronavirus viral protein virus RNA Betacoronavirus chemistry cryoelectron microscopy drug effect enzyme active site enzymology metabolism molecular model physiology protein conformation virus replication Adenosine Monophosphate Alanine Antiviral Agents Betacoronavirus Catalytic Domain Cryoelectron Microscopy Enzyme Inhibitors Models, Molecular Multiprotein Complexes Protein Conformation RNA Replicase RNA, Viral Viral Nonstructural Proteins Virus Replication
语种	英语
来源机构	Science (New York, N.Y.)
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/133402
推荐引用方式 GB/T 7714	Yin W.,Mao C.,Luan X.,et al. Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir[J]. Science (New York, N.Y.),2020,368(6498).
APA	Yin W..,Mao C..,Luan X..,Shen D.-D..,Shen Q..,...&Xu H.E..(2020).Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir.,368(6498).
MLA	Yin W.,et al."Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir".368.6498(2020).