SARS-CoV-2 uses ACE2 (angiotensin-converting enzyme 2) as receptor to enter host cells.
ACE2 is a regulator of the renin-angiotensin system (RAS) and is widely expressed in the organs affected in COVID-19 patients including lungs, kidneys, cardiovascular system, gut, and the central nervous system [PMID:32264791].
The main function of ACE2 is the conversion of angiotensin II (AngII) to angiotensin 1-7 (Ang1-7). These two angiotensins trigger counter-regulatory arms of the RAS [PMID:31427727]. The signaling via AngII and its receptor AGTR1 induces vasoconstriction, oxidative stress and inflammation, while the signaling via Ang1-7 and its receptors MAS1 and MRGPRD attenuate these effects [PMID:31427727]. In SARS-CoV2 patients AngII levels are elevated, promoting the harmful signalling via AngII/AGTR1 [PMID:32048163; 32336612].
RAS, is tightly regulated and influenced by factors known to increase the risk to develop severe forms of COVID-19, such as hypertension [PMID:18403595], male sex [PMID:26010093], or aging [PMID:28174624]. The role of the RAS in the pathogenesis of COVID-19 and the effects of RAS-inhibiting drugs on the risk of COVID-19 infection and disease progression are currently under investigation.
This SARS-CoV-2 renin-angiotensin system network has been generated in collaboration with the Covid-19 Disease map.