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Structure paper

TitleStructural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir.
Journal, issue, pagesScience, Vol. 368, Issue 6498, Page 1499-1504, Year 2020
Publish dateJun 26, 2020
AuthorsWanchao Yin / Chunyou Mao / Xiaodong Luan / Dan-Dan Shen / Qingya Shen / Haixia Su / Xiaoxi Wang / Fulai Zhou / Wenfeng Zhao / Minqi Gao / Shenghai Chang / Yuan-Chao Xie / Guanghui Tian / He-Wei Jiang / Sheng-Ce Tao / Jingshan Shen / Yi Jiang / Hualiang Jiang / Yechun Xu / Shuyang Zhang / Yan Zhang / H Eric Xu /
PubMed AbstractThe 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 ...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.
External linksScience / PubMed:32358203 / PubMed Central
MethodsEM (single particle)
Resolution2.5 - 2.8 Å
Structure data

30209

7bv1

EMDB-30209, PDB-7bv1:
Cryo-EM structure of the apo nsp12-nsp7-nsp8 complex
Method: EM (single particle) / Resolution: 2.8 Å

30210

7bv2

EMDB-30210, PDB-7bv2:
The nsp12-nsp7-nsp8 complex bound to the template-primer RNA and triphosphate form of Remdesivir(RTP)
Method: EM (single particle) / Resolution: 2.5 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-POP:
PYROPHOSPHATE 2- / Pyrophosphate

ChemComp-MG:
Unknown entry

ChemComp-F86:
[(2~{R},3~{S},4~{R},5~{R})-5-(4-azanylpyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-bis(oxidanyl)oxolan-2-yl]methyl dihydrogen phosphate / medication, antivirus*YM / Remdesivir

ChemComp-HOH:
WATER / Water

Source
  • SARS bat coronavirus
  • severe acute respiratory syndrome coronavirus 2
KeywordsVIRAL PROTEIN / SARS-CoV-2 / RNA Polymerase / Apo / Remdesivir

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