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Patrick Cramer1, Goran Kokic1, Christian Dienemann1

  • 1Abteilung Molekularbiologie, Max-Planck-Institut für biophysikalische Chemie, Am Fassberg 11, D-37077 Göttingen, Deutschland.

Biospektrum : Zeitschrift Der Gesellschaft Fur Biologishe Chemie (GBCH) Und Der Vereinigung Fur Allgemeine Und Angewandte Mikrobiologie (VAAM)
|February 22, 2021
PubMed
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Coronaviruses rely on RNA-dependent RNA polymerase for genome replication. Structural studies reveal SARS-CoV-2 polymerase function and inhibition by remdesivir, a COVID-19 treatment.

Area of Science:

  • Molecular biology
  • Virology
  • Structural biology

Context:

  • Coronaviruses, including SARS-CoV-2, possess a unique RNA-dependent RNA polymerase (RdRp) essential for their life cycle.
  • Understanding the RdRp structure and function is critical for developing antiviral therapies against COVID-19.

Purpose:

  • To elucidate the structural basis of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) activity.
  • To explain the mechanism of viral RNA synthesis and genome replication.
  • To investigate the interaction between the viral polymerase and remdesivir.

Summary:

  • The structure of the SARS-CoV-2 RNA-dependent RNA polymerase was determined using cryo-electron microscopy.
  • The determined structure provides insights into the enzyme's processive RNA synthesis and replication of the large viral genome.

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  • Recent studies reveal how remdesivir inhibits the viral polymerase, offering a mechanistic explanation for its therapeutic effect in COVID-19.

    • Impact:

    • Provides a structural foundation for understanding coronavirus RNA replication.
    • Facilitates the rational design of novel antiviral drugs targeting the viral polymerase.
    • Enhances knowledge of remdesivir's mechanism of action against SARS-CoV-2.