A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor

The recent emergence of coronavirus disease-2019 (COVID-19) as a global pandemic has prompted scientists to address an urgent need for defining mechanisms of disease pathology and treatment. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent for COVID-19, employs angiotensin converting enzyme 2 (ACE2) as its primary target for cell surface attachment and likely entry into the host cell. Thus, understanding factors that may regulate the expression and function of ACE2 in the healthy and diseased body is critical for clinical intervention. Over 66% of all adults in the United States are currently using a prescription drug and while earlier findings have focused on possible upregulation of ACE2 expression through the use of renin angiotensin system (RAS) inhibitors, mounting evidence suggests that various other widely administered drugs used in the treatment of hypertension, heart failure, diabetes mellitus, hyperlipidemias, coagulation disorders, and pulmonary disease may also present a varied risk for COVID-19. Specifically, we summarize mechanisms on how heparin, statins, steroids and phytochemicals, besides their established therapeutic effects, may also interfere with SARS-CoV-2 viral entry into cells. We also describe evidence on the effect of several vitamins, phytochemicals, and naturally occurring compounds on ACE2 expression and activity in various tissues and disease models. This comprehensive review aims to provide a timely compendium on the potential impact of commonly prescribed drugs and pharmacologically active compounds on COVID-19 pathology and risk through regulation of ACE2 and RAS signaling.