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Structural and Biochemical Characterization of the nsp12-nsp7-nsp8 Core Polymerase Complex from SARS-CoV-2.
Peng, Qi; Peng, Ruchao; Yuan, Bin; Zhao, Jingru; Wang, Min; Wang, Xixi; Wang, Qian; Sun, Yan; Fan, Zheng; Qi, Jianxun; Gao, George F; Shi, Yi.
  • Peng Q; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
  • Peng R; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
  • Yuan B; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of the Chinese Academy of Sciences, Beijing 100049, China.
  • Zhao J; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of the Chinese Academy of Sciences, Beijing 100049, China.
  • Wang M; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
  • Wang X; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
  • Wang Q; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of the Chinese Academy of Sciences, Beijing 100049, China.
  • Sun Y; Savaid Medical School, University of the Chinese Academy of Sciences, Beijing 100049, China.
  • Fan Z; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
  • Qi J; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of the Chinese Academy of Sciences, Beijing 100049, China; Center for Influenza Research and Early Warning (CASCIRE), CAS-TWA
  • Gao GF; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of the Chinese Academy of Sciences, Beijing 100049, China; Center for Influenza Research and Early Warning (CASCIRE), CAS-TWA
  • Shi Y; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of the Chinese Academy of Sciences, Beijing 100049, China; Center for Influenza Research and Early Warning (CASCIRE), CAS-TWA
Cell Rep ; 31(11): 107774, 2020 06 16.
Article in English | MEDLINE | ID: covidwho-594914
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ABSTRACT
The ongoing global pandemic of coronavirus disease 2019 (COVID-19) has caused a huge number of human deaths. Currently, there are no specific drugs or vaccines available for this virus (SARS-CoV-2). The viral polymerase is a promising antiviral target. Here, we describe the near-atomic-resolution structure of the SARS-CoV-2 polymerase complex consisting of the nsp12 catalytic subunit and nsp7-nsp8 cofactors. This structure highly resembles the counterpart of SARS-CoV with conserved motifs for all viral RNA-dependent RNA polymerases and suggests a mechanism of activation by cofactors. Biochemical studies reveal reduced activity of the core polymerase complex and lower thermostability of individual subunits of SARS-CoV-2 compared with SARS-CoV. These findings provide important insights into RNA synthesis by coronavirus polymerase and indicate adaptation of SARS-CoV-2 toward humans with a relatively lower body temperature than the natural bat hosts.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA-Dependent RNA Polymerase / Viral Nonstructural Proteins / Cryoelectron Microscopy / Betacoronavirus Topics: Vaccines Language: English Journal: Cell Rep Year: 2020 Document Type: Article Affiliation country: J.celrep.2020.107774

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Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA-Dependent RNA Polymerase / Viral Nonstructural Proteins / Cryoelectron Microscopy / Betacoronavirus Topics: Vaccines Language: English Journal: Cell Rep Year: 2020 Document Type: Article Affiliation country: J.celrep.2020.107774