Developing new drugs that activate the protective arm of the renin-angiotensin system as a potential treatment for respiratory failure in COVID-19 patients

Drug Discov Today. 2021 May;26(5):1311-1318. doi: 10.1016/j.drudis.2021.02.010. Epub 2021 Feb 17.

Abstract

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has reached pandemic proportions with negative impacts on global health, the world economy and human society. The clinical picture of COVID-19, and the fact that Angiotensin converting enzyme 2 (ACE2) is a receptor of SARS-CoV-2, suggests that SARS-CoV-2 infection induces an imbalance in the renin-angiotensin system (RAS). We review clinical strategies that are attempting to rebalance the RAS in COVID-19 patients by using ACE inhibitors, angiotensin receptor blockers, or agonists of angiotensin-II receptor type 2 or Mas receptor (MasR). We also propose that the new MasR activator BIO101, a pharmaceutical grade formulation of 20-hydroxyecdysone that has anti-inflammatory, anti-fibrotic and cardioprotective properties, could restore RAS balance and improve the health of COVID-19 patients who have severe pneumonia.

Publication types

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

MeSH terms

  • Angiotensin Receptor Antagonists / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Animals
  • COVID-19 / metabolism
  • COVID-19 / virology
  • COVID-19 Drug Treatment*
  • Commelinaceae
  • Drug Development
  • Ecdysone / analogs & derivatives
  • Ecdysone / therapeutic use
  • Host-Pathogen Interactions
  • Humans
  • Plant Extracts / therapeutic use
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins / agonists
  • Proto-Oncogene Proteins / metabolism
  • Receptors, G-Protein-Coupled / agonists
  • Receptors, G-Protein-Coupled / metabolism
  • Renin-Angiotensin System / drug effects*
  • SARS-CoV-2 / metabolism
  • SARS-CoV-2 / pathogenicity*

Substances

  • 20-hydroxylecdysone
  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • MAS1 protein, human
  • Plant Extracts
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • Receptors, G-Protein-Coupled
  • Ecdysone