Structural and Biochemical Characterization of the nsp12-nsp7-nsp8 Core Polymerase Complex from SARS-CoV-2

• 出版年: Cell Reports
• 主要な著者: Qi Peng, Ruchao Peng, Bin Yuan, Jingru Zhao, Min Wang, Xixi Wang, Qian Wang, Yan Sun, Zheng Fan, Jianxun Qi, George F. Gao, Yi Shi
• フォーマット: 論文
• 言語: 英語
• 出版事項: Elsevier 2020-06-01
• 主題: SARS-CoV-2; non-structural proteins; polymerase; cofactors; RNA synthesis; cryo-EM
• オンライン･アクセス: http://www.sciencedirect.com/science/article/pii/S2211124720307543
• ISSN: 2211-1247

Summary: 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.