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

被引:199
作者
Peng, Qi [1 ]
Peng, Ruchao [1 ]
Yuan, Bin [1 ,2 ]
Zhao, Jingru [1 ,2 ]
Wang, Min [1 ]
Wang, Xixi [1 ]
Wang, Qian [1 ,2 ]
Sun, Yan [2 ]
Fan, Zheng [1 ]
Qi, Jianxun [1 ,2 ,3 ]
Gao, George F. [1 ,2 ,3 ]
Shi, Yi [1 ,2 ,3 ,4 ,5 ]
机构
[1] Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing 100101, Peoples R China
[2] Univ Chinese Acad Sci, Savaid Med Sch, Beijing 100049, Peoples R China
[3] Chinese Acad Sci, Ctr Influenza Res & Early Warning CASCIRE, CAS TWAS Ctr Excellence Emerging Infect Dis CEEID, Beijing 100101, Peoples R China
[4] Univ Chinese Acad Sci, Chongqing Gen Hosp, Chongqing Key Lab Neurodegenerat Dis, Chongqing 400013, Peoples R China
[5] Jilin Univ, Coll Basic Med, Changchun 130021, Jilin, Peoples R China
基金
中国国家自然科学基金;
关键词
DEPENDENT RNA-POLYMERASE; CRYSTAL-STRUCTURE; SARS; INSIGHTS; REPLICATION; PROTEIN;
D O I
10.1016/j.celrep.2020.107774
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 SARSCoV-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.
引用
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页数:14
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