Targeting SARS-CoV-2 viral proteases as a therapeutic strategy to treat COVID-19

J Med Virol. 2021 May;93(5):2722-2734. doi: 10.1002/jmv.26814. Epub 2021 Feb 9.

Abstract

The 21st century has witnessed three outbreaks of coronavirus (CoVs) infections caused by severe acute respiratory syndrome (SARS)-CoV, Middle East respiratory syndrome (MERS)-CoV, and SARS-CoV-2. Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, spreads rapidly and since the discovery of the first COVID-19 infection in December 2019, has caused 1.2 million deaths worldwide and 226,777 deaths in the United States alone. The high amino acid similarity between SARS-CoV and SARS-CoV-2 viral proteins supports testing therapeutic molecules that were designed to treat SARS infections during the 2003 epidemic. In this review, we provide information on possible COVID-19 treatment strategies that act via inhibition of the two essential proteins of the virus, 3C-like protease (3CLpro ) or papain-like protease (PLpro ).

Keywords: 3 chymotrypsin-like cysteine protease; COVID-19; SARS coronavirus; SARS-CoV-2; coronavirus main protease; papain-like cysteine protease.

Publication types

  • Review

MeSH terms

  • Antiviral Agents / therapeutic use*
  • COVID-19 / epidemiology
  • COVID-19 Drug Treatment*
  • Coronavirus 3C Proteases / chemistry
  • Coronavirus 3C Proteases / drug effects
  • Coronavirus 3C Proteases / genetics
  • Coronavirus Papain-Like Proteases / chemistry
  • Coronavirus Papain-Like Proteases / drug effects
  • Coronavirus Papain-Like Proteases / genetics
  • Humans
  • Middle East Respiratory Syndrome Coronavirus
  • Protease Inhibitors / therapeutic use
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / metabolism
  • Viral Nonstructural Proteins / chemistry
  • Viral Nonstructural Proteins / genetics
  • Viral Proteases / drug effects*

Substances

  • Antiviral Agents
  • Protease Inhibitors
  • Viral Nonstructural Proteins
  • Viral Proteases
  • 3C-like protease, SARS coronavirus
  • Coronavirus Papain-Like Proteases
  • papain-like protease, SARS-CoV-2
  • Coronavirus 3C Proteases