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Letter regarding: Another strategy for off-target ACE2
  • Artemio García-Escobar
Artemio García-Escobar
La Luz Hospital

Corresponding Author:[email protected]

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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.