The main protease and RNA-dependent RNA polymerase are two prime targets for SARS-CoV-2

Biochem Biophys Res Commun. 2021 Jan 29:538:63-71. doi: 10.1016/j.bbrc.2020.10.091. Epub 2020 Nov 21.

Abstract

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses an unprecedented global health crisis. It is particularly urgent to develop clinically effective therapies to contain the pandemic. The main protease (Mpro) and the RNA-dependent RNA polymerase (RdRP), which are responsible for the viral polyprotein proteolytic process and viral genome replication and transcription, respectively, are two attractive drug targets for SARS-CoV-2. This review summarizes up-to-date progress in the structural and pharmacological aspects of those two key targets above. Different classes of inhibitors individually targeting Mpro and RdRP are discussed, which could promote drug development to treat SARS-CoV-2 infection.

Keywords: Inhibitors; Main protease; RNA-dependent RNA polymerase; SARS-CoV-2.

Publication types

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

MeSH terms

  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology
  • Coronavirus 3C Proteases / antagonists & inhibitors*
  • Coronavirus 3C Proteases / chemistry*
  • Coronavirus Protease Inhibitors / chemistry*
  • Coronavirus Protease Inhibitors / pharmacology
  • Coronavirus RNA-Dependent RNA Polymerase / antagonists & inhibitors*
  • Coronavirus RNA-Dependent RNA Polymerase / chemistry*
  • Drug Design
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Protein Conformation
  • SARS-CoV-2 / drug effects
  • SARS-CoV-2 / enzymology*

Substances

  • Antiviral Agents
  • Coronavirus Protease Inhibitors
  • Enzyme Inhibitors
  • Coronavirus RNA-Dependent RNA Polymerase
  • Coronavirus 3C Proteases