Structural and Biochemical Characterization of the nsp12-nsp7-nsp8 Core Polymerase Complex from SARS-CoV-2
Copyright policy )Structural and Biochemical Characterization of the nsp12-nsp7-nsp8 Core Polymerase Complex from SARS-CoV-2
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.
- University of Chinese Academy of Sciences China (People's Republic of)
- Chinese Academy of Sciences China (People's Republic of)
- Jilin University China (People's Republic of)
- Institute of Microbiology China (People's Republic of)
Models, Molecular, Coronavirus RNA-Dependent RNA Polymerase, QH301-705.5, SARS-CoV-2, Cryoelectron Microscopy, Viral Nonstructural Proteins, RNA-Dependent RNA Polymerase, General Biochemistry, Genetics and Molecular Biology, Article, polymerase, Evolution, Molecular, Betacoronavirus, Amino Acid Substitution, Severe acute respiratory syndrome-related coronavirus, non-structural proteins, Multiprotein Complexes, cofactors, Escherichia coli, cryo-EM, RNA synthesis, Biology (General)
Models, Molecular, Coronavirus RNA-Dependent RNA Polymerase, QH301-705.5, SARS-CoV-2, Cryoelectron Microscopy, Viral Nonstructural Proteins, RNA-Dependent RNA Polymerase, General Biochemistry, Genetics and Molecular Biology, Article, polymerase, Evolution, Molecular, Betacoronavirus, Amino Acid Substitution, Severe acute respiratory syndrome-related coronavirus, non-structural proteins, Multiprotein Complexes, cofactors, Escherichia coli, cryo-EM, RNA synthesis, Biology (General)
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