Angiotensin Converting Enzyme 2 in Cardiopulmonary Diseases: Ramifications for the Control of SARS-CoV-2

Abstract

Discovery of angiotensin converting enzyme 2 (ACE2) revealed that the renin angiotensin system (RAS) has two counterbalancing arms. ACE2 is a major player in the protective arm, highly expressed in lungs and gut with the ability to mitigate cardiopulmonary diseases such as inflammatory lung disease. ACE2 also exhibits activities involving gut microbiome, nutrition, and as a chaperone stabilizing the neutral amino acid transporter, B0AT1, in gut. But the current interest in ACE2 arises because it is the cell surface receptor for the novel coronavirus, SARS-CoV-2, to infect host cells, similar to SARS-CoV. This suggests that ACE2 be considered harmful, however because of its important other roles, it is paradoxically a potential therapeutic target for cardiopulmonary diseases including COVID-19, caused by SARS-CoV-2. This review describes the discovery of ACE2, its physiological functions, and its place in the RAS. It illustrates new analyses of the structure of ACE2 that provides better understanding of its actions particularly in lung and gut, shedding of ACE2 by ADAM17 and role of TMPRSS2 in SARS-CoV-2 entry into host cells. Cardiopulmonary diseases are associated with decreased ACE2 activity and the mitigation by increasing ACE2 activity along with its therapeutic relevance are addressed. Finally, the potential use of ACE2 as a treatment target in COVID-19, despite its role to allow viral entry into host cells, is suggested.