Role of the Backbenchers of the Renin-Angiotensin System ACE2 and AT2 Receptors in COVID-19: Lessons From SARS

Gumashta, Jyotsna; Gumashta, Raghvendra

The novel coronaviruses causing severe acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19) have been shown to utilize angiotensin-converting enzyme 2 (ACE2) as the receptor for entry into the host cells. The involvement of the renin-angiotensin system (RAS) in the evolution and pathogenesis of lung diseases has been implicated in recent years. The two enzymes of RAS, angiotensin-converting enzyme (ACE) and ACE2, serve a contrasting function. ACE helps in the formation of angiotensin II (AGII) from angiotensin I (AGI), and ACE2 cleaves AGI and AGII into AG (1-9) and AG (1-7) respectively. The ACE-induced AGII has vasoconstrictor and pro-inflammatory properties via AT1R, whereas ACE2 has been shown to protect against lung injury. The less spoken about AGII receptor, angiotensin receptor type 2 (AT2R), has anti-inflammatory and anti-fibrotic effects in lung tissue and may be of significance in light of the lung pathology presentation in COVID-19. A review of articles searched in PubMed and peer-reviewed journals of importance was done using search terms “ACE2,” “AT2,” “SARS,” and COVID-19.” Lung involvement in both SARS and COVID-19 has been very severe and suggestive of severe inflammatory and immune reactions. Animal studies have shown that ACE2 and AT2 receptors counter the pro-inflammatory and other effects mediated by angiotensin II by their vasodilator, anti-inflammatory, anti-fibrotic, and anti-proliferative effects. They have been shown to protect against and revert acute lung injuries. The instrumental role of recombinant ACE2, AT2 receptor agonists, and AT1 receptor blockers may be helpful in the treatment of COVID-19.