Enzyme inhibition as a potential therapeutic strategy to treat COVID-19 infection

Bioorg Med Chem. 2021 Oct 15:48:116389. doi: 10.1016/j.bmc.2021.116389. Epub 2021 Sep 14.

Abstract

With the emergence of the third infectious and virulent coronavirus within the past two decades, it has become increasingly important to understand how the virus causes infection. This will inform therapeutic strategies that target vulnerabilities in the vital processes through which the virus enters cells. This review identifies enzymes responsible for SARS-CoV-2 viral entry into cells (ACE2, Furin, TMPRSS2) and discuss compounds proposed to inhibit viral entry with the end goal of treating COVID-19 infection. We argue that TMPRSS2 inhibitors show the most promise in potentially treating COVID-19, in addition to being a pre-existing medication with fewer predicted side-effects.

Keywords: ACE2; COVID-19; Coronavirus; Enzymes; Furin; Inhibition; RAAS; SARS-CoV-2; Spike protein; TMPRSS2.

Publication types

  • Review

MeSH terms

  • Angiotensin Receptor Antagonists / therapeutic use*
  • Angiotensin-Converting Enzyme 2 / antagonists & inhibitors*
  • Animals
  • Antiviral Agents / therapeutic use*
  • COVID-19 Drug Treatment*
  • Drug Combinations
  • Humans
  • Janus Kinase Inhibitors / therapeutic use*
  • Methotrexate / therapeutic use
  • Receptors, Angiotensin / metabolism
  • SARS-CoV-2 / drug effects*
  • Signal Transduction / drug effects

Substances

  • Angiotensin Receptor Antagonists
  • Antiviral Agents
  • Drug Combinations
  • Janus Kinase Inhibitors
  • Receptors, Angiotensin
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Methotrexate