RNA-dependent RNA polymerase of SARS-CoV-2 as a therapeutic target

J Med Virol. 2021 Jan;93(1):300-310. doi: 10.1002/jmv.26264. Epub 2020 Jul 19.

Abstract

The global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), named coronavirus disease 2019, has infected more than 8.9 million people worldwide. This calls for urgent effective therapeutic measures. RNA-dependent RNA polymerase (RdRp) activity in viral transcription and replication has been recognized as an attractive target to design novel antiviral strategies. Although SARS-CoV-2 shares less genetic similarity with SARS-CoV (~79%) and Middle East respiratory syndrome coronavirus (~50%), the respective RdRps of the three coronaviruses are highly conserved, suggesting that RdRp is a good broad-spectrum antiviral target for coronaviruses. In this review, we discuss the antiviral potential of RdRp inhibitors (mainly nucleoside analogs) with an aim to provide a comprehensive account of drug discovery on SARS-CoV-2.

Keywords: COVID-19; RdRp; SARS-CoV-2; coronavirus; drug target.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use*
  • COVID-19 / virology*
  • COVID-19 Drug Treatment*
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use*
  • Nucleosides / pharmacology
  • Nucleosides / therapeutic use
  • RNA-Dependent RNA Polymerase / antagonists & inhibitors*
  • RNA-Dependent RNA Polymerase / genetics
  • RNA-Dependent RNA Polymerase / metabolism
  • SARS-CoV-2 / enzymology*
  • SARS-CoV-2 / metabolism

Substances

  • Antiviral Agents
  • Enzyme Inhibitors
  • Nucleosides
  • RNA-Dependent RNA Polymerase