Regulation of Angiotensin-Converting Enzyme 2: A Potential Target to Prevent COVID-19?

Figures

• 

  Figure 1. Renin–angiotensin system. Renin cleaves angiotensinogen to form Ang I, which is then cleaved by angiotensin-converting enzyme (ACE) to generate Ang II. Ang II can bind to Ang II type 1 and 2 receptors (AT1/2R). ACE2 is a single transmembrane protein, which can recognize Ang I and cleave it into Ang 1-9, which is quickly converted to Ang 1-7 by ACE. Moreover, Ang-(1-7) has been identified as a ligand for Mas receptor, which is a seven-transmembrane G-protein coupled receptor. Mas receptor may induce intracellular signaling cascades such as protein kinase B and induction of nitric oxide (NO) production.

• 

  Figure 2. Roles of angiotensin-converting enzyme 2 (ACE2) in severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 infection. (A) ACE2 acts as the key receptor in avian influenza H5N1 and H7N9 virus infections as well as in SARS-CoV and SARS-CoV-2 infections. (B) Roles of a soluble form of angiotensin-converting enzyme 2 (sACE2) and A disintegrin and metalloprotease 17 (ADAM17) in cells infected with SARS-CoV and SARS-CoV-2. ADAM17 cleaves ACE2 and forms a 20-amino acid transmembrane peptide. The binding of Ang II with AT1R promotes sACE2 formation by increasing ADAM17 activity, which generates sACE2 and binds to the spike protein of SARS-CoV-2 as the virus receptor.