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.