The fight against COVID-19: Striking a balance in the renin-angiotensin system

Drug Discov Today. 2021 Oct;26(10):2214-2220. doi: 10.1016/j.drudis.2021.04.006. Epub 2021 Apr 15.

Abstract

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells by interacting with membrane-bound angiotensin-converting enzyme 2 (ACE2), a vital element in the renin-angiotensin system (RAS), which regulates blood pressure, fluid balance, and cardiovascular functions. We herein evaluate existing evidence for the molecular alterations within the RAS pathway (e.g., ACE2 and angiotensin II) during SARS-CoV-2 infection and subsequent Coronavirus Disease 2019 (COVID-19). This includes reports regarding potential effect of RAS blockade (e.g., ACE inhibitors and angiotensin II receptor blockers) on ACE2 expression and clinical outcomes in patients with co-morbidities commonly treated with these agents. The collective evidence suggests a dual role for ACE2 in COVID-19, depending on the stage of infection and the coexisting diseases in individual patients. This information is further discussed with respect to potential therapeutic strategies targeting RAS for COVID-19 treatment.

Keywords: Angiotensin II (Ang II); Angiotensin-converting enzyme 2 (ACE2); COVID-19; RAS blockade; Renin-angiotensin system (RAS); SARS-CoV-2.

Publication types

  • Review

MeSH terms

  • Angiotensin II / metabolism
  • Angiotensin-Converting Enzyme 2 / genetics
  • COVID-19 / physiopathology
  • COVID-19 / therapy*
  • COVID-19 Drug Treatment
  • Humans
  • Renin-Angiotensin System / drug effects*
  • SARS-CoV-2

Substances

  • Angiotensin II
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2