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.
Mesh Terms:
Amino Acid Substitution, Betacoronavirus, Coronavirus RNA-Dependent RNA Polymerase, Cryoelectron Microscopy, Escherichia coli, Evolution, Molecular, Models, Molecular, Multiprotein Complexes, RNA-Dependent RNA Polymerase, SARS Virus, SARS-CoV-2, Viral Nonstructural Proteins
Amino Acid Substitution, Betacoronavirus, Coronavirus RNA-Dependent RNA Polymerase, Cryoelectron Microscopy, Escherichia coli, Evolution, Molecular, Models, Molecular, Multiprotein Complexes, RNA-Dependent RNA Polymerase, SARS Virus, SARS-CoV-2, Viral Nonstructural Proteins
Cell Rep
Date: Dec. 16, 2019
PubMed ID: 32531208
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