Figure 1. ACE2 function and its regulation in SARS-CoV2 infection.
ACE2 is a carboxypeptidases which catalyzes and inactivates Angiotensin I and Angiotensin II, respectively, into the vasodilator peptides Angiotensin 1–9 and Angiotensin 1–7, which bind Mas receptor (MasR) leading to reduced inflammation and vasodilation. ACE2 also cleaves des-Arg9bradykinin (DABK), a bioactive kinin derived from kininogen pathway, into inactive metabolites. ACE2 is the cell entry receptor for SARS-CoV2; the binding of viral spike glycoprotein with ACE2 and the priming of the spike through the transmembrane protease serine 2 (TMPRSS2), leads to SARS-CoV2 infection. The binding of SARS-CoV2 downregulates ACE2 expression, leading to a reduction of its enzymatic activity and the ensuing increase of Angiotensin II and DABK levels. Angiotensin II takes its deleterious effect by binding the Angiotensin II type 1 receptor (AT1R), whereas DABK concurs to inflammation by binding BK receptor B1 (B1R), resulting in severe lung injury, pulmonary inflammation and edema, increased coagulation, hypertension and cardiac hypertrophy, which are all features of COVID-19 patients.