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

•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.