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

• Published in: Drug discovery today Vol. 26; no. 5; pp. 1311 - 1318
• Main Authors: Latil, Mathilde, Camelo, Serge, Veillet, Stanislas, Lafont, René, Dilda, Pierre J.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2021
• Subjects: Angiotensin Receptor Antagonists - therapeutic use; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Animals; Commelinaceae; COVID-19 - metabolism; COVID-19 - virology; COVID-19 Drug Treatment; 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; Review; SARS-CoV-2 - metabolism; SARS-CoV-2 - pathogenicity
• ISSN: 1359-6446; 1878-5832
• DOI: 10.1016/j.drudis.2021.02.010

•SARS-CoV-2 infection induces an imbalance in the renin–angiotensin system.•We present current clinical strategies that attempt to rebalance the RAS in COVID-19 patients.•There is interest in stimulating the protective arm of the RAS in COVID-19 patients.•20-Hydroxyecdysone, a Mas receptor (MasR) activator, has potential for the treatment of COVID-19. 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. By rebalancing the renin–angiotensin system (RAS), BIO101 (20-hydroxyecdysone) could improve cardio-respiratory functions, limit the requirement for mechanical ventilation and reduce mortality in severely ill COVID-19 patients who are infected by SARS-CoV-2.