Targeting Proteases for Treating COVID-19

J Proteome Res. 2020 Nov 6;19(11):4316-4326. doi: 10.1021/acs.jproteome.0c00430. Epub 2020 Oct 22.

Abstract

The unprecedented pandemic of coronavirus disease 2019 (COVID-19) demands effective treatment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The infection of SARS-CoV-2 critically depends on diverse viral or host proteases, which mediate viral entry, viral protein maturation, as well as the pathogenesis of the viral infection. Endogenous and exogenous agents targeting for proteases have been proved to be effective toward a variety of viral infections ranging from HIV to influenza virus, suggesting protease inhibitors as a promising antiviral treatment for COVID-19. In this Review, we discuss how host and viral proteases participated in the pathogenesis of COVID-19 as well as the prospects and ongoing clinical trials of protease inhibitors as treatments.

Keywords: ACE2; COVID-19; SARS-CoV-2; TMPRSS2; main protease.

Publication types

  • Review

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Antiviral Agents*
  • Betacoronavirus* / drug effects
  • Betacoronavirus* / enzymology
  • COVID-19
  • Coronavirus Infections* / drug therapy
  • Coronavirus Infections* / physiopathology
  • Coronavirus Infections* / virology
  • Host-Pathogen Interactions
  • Humans
  • Pandemics*
  • Peptide Hydrolases
  • Peptidyl-Dipeptidase A
  • Pneumonia, Viral* / drug therapy
  • Pneumonia, Viral* / physiopathology
  • Pneumonia, Viral* / virology
  • Protease Inhibitors*
  • SARS-CoV-2
  • Serine Endopeptidases
  • Viral Proteins

Substances

  • Antiviral Agents
  • Protease Inhibitors
  • Viral Proteins
  • Peptide Hydrolases
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Serine Endopeptidases
  • TMPRSS2 protein, human