Abstract
The angiotensin-converting enzyme 2 (ACE2) is a type I integral membrane
protein (amino acids 805) that contains a transmembrane domain (amino
acids 740-763) and extracellular region (ectodomain). The extracellular
region is composed of a metalloprotease zinc-binding site (amino acids
374-378, HEMGH) that is the single catalytic domain of the ACE2. The
ACE2 ectodomain undergoes shedding by a disintegrin and
metalloproteinase domain‐containing protein 17 a protease up-regulated
in heart failure (HF) consequently releases a soluble form of ACE2.
Increasing soluble ACE2 levels are associated with HF, adverse cardiac
remodelling and correlated with B-type natriuretic peptide levels. The
spike protein (S) of severe acute respiratory syndrome coronavirus 1
(SARS-CoV) attaches the virus to its cellular receptor ACE2. The
structural analysis demonstrated that S subunit 1 (S1) and the
C-terminal domain of the SARS-CoV-2, otherwise known as the
receptor-binding domain, bound to soluble ectodomain protein of human
ACE2. The construction of a fusion protein consisting of the
extracellular domain of human ACE2 linked to the fragment crystallisable
region (Fc) domain of human IgG1 (ACE2-Ig), the ACE2 variant in which
two active-site histidines have been altered to asparagines (mACE2-Ig),
and the inhibition of metalloproteinase with chelator agents that
removes zinc that leads disrupting the catalytic site of the ACE2
ectodomain which is indispensable for the Covid-19 attachment could be
another promising potential therapeutic approach.