Urgent need for evaluating agonists of Angiotensin-(1-7)/ Mas receptor axis for treatment of patients with COVID-19

Shete, Ashwini

Abstract ACE2 being a receptor of entry of SARS-CoV-2 into the host cells, its upregulation has been implicated in increasing susceptibility of individuals to the infections. Clinical picture of COVID-19 suggests a role ACE2 blockade, rather than its overexpression, in causing the pathogenesis. ACE2 blockade results in increased Angiotensin II activity with simultaneous hampering of functions of Angiotensin-(1-7)/MasR axis. Acute respiratory distress due to interstitial pulmonary fibrosis, cardiomyopathy and shock reported in COVID-19 patients can be explained by imbalanced Angiotensin II and Angiotensin-(1-7) activities. Failure of Angiotensin II type 1 receptor blockers to control severity of SARS-CoV-2 infections indicates importance of simultaneous induction of Angiotensin-(1-7)/MasR axis for correcting pathological conditions in COVID-19 through its anti-fibrotic, anti-inflammatory, vasodilatory and cardioprotective roles. MasR agonists have also shown organ protective effects in a number of animal studies. Unfortunately, these agonists have not been tested in clinical studies. Their urgent evaluation in seriously ill COVID-19 patients is urgently warranted to reduce mortality due to the infections.