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

Qi Peng1, Ruchao Peng1, Bin Yuan2

  • 1CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.

Cell Reports
|June 13, 2020
PubMed

Insights

Researchers determined the structure of the SARS-CoV-2 polymerase complex, revealing insights into viral RNA synthesis. This finding offers potential for developing new antiviral therapies against COVID-19.

Area of Science:

  • Structural Biology
  • Virology
  • Biochemistry

Background:

  • The COVID-19 pandemic caused by SARS-CoV-2 has led to significant mortality globally.
  • No specific antiviral drugs or vaccines are currently available for SARS-CoV-2.
  • Viral RNA-dependent RNA polymerase is a key target for antiviral drug development.

Purpose of the Study:

  • To determine the near-atomic-resolution structure of the SARS-CoV-2 polymerase complex.
  • To understand the role of nsp7-nsp8 cofactors in polymerase activation.
  • To compare the biochemical properties of SARS-CoV-2 polymerase with SARS-CoV polymerase.

Main Methods:

  • X-ray crystallography to determine the polymerase complex structure.
  • Biochemical assays to assess polymerase activity and thermostability.

Main Results:

  • The near-atomic-resolution structure of the SARS-CoV-2 polymerase complex (nsp12, nsp7, nsp8) was elucidated.
  • The structure is highly conserved compared to SARS-CoV polymerase, with conserved motifs for RNA-dependent RNA polymerases.
  • Cofactors nsp7-nsp8 appear to activate the polymerase.
  • SARS-CoV-2 polymerase exhibited reduced activity and lower thermostability compared to SARS-CoV.
  • Findings suggest SARS-CoV-2 adaptation to human hosts with lower body temperatures.

Conclusions:

  • The determined structure provides critical insights into coronavirus RNA synthesis.
  • The observed differences in polymerase activity and stability may reflect host adaptation.
  • This structural and biochemical data can inform the development of targeted antiviral strategies against SARS-CoV-2.
Keywords:
RNA synthesisSARS-CoV-2cofactorscryo-EMnon-structural proteinspolymerase

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