Inhibition of ACE1
The ability of ACE1 to generate ANG II is a critical step in providing the “driver” for multiple features of the pathophysiology of COVID-19. ACE1 (also known as dipeptidyl carboxypeptidase 1) is a zinc metalloenzyme that removes a dipeptide from the C-terminus of certain peptides, including His-Leu from the inactive decapeptide ANG I to generate ANG II, the active octapeptide. ACE inhibitors approved for clinical use are competitive peptide antagonists that blunt ANG II formation but also the cleavage by ACE1 of the peptide bradykinin. We have found no studies that assessed the efficacy of ACE1 inhibitors in SARS-1 infections. The decrease in ANG II formation would likely be beneficial in such infections. However, since a substantial proportion (~20%) of patients administered ACEIs develop cough as a side effect (generally attributed to an increase in bradykinin) and dry cough is a feature of COVID-19 infection, this is a potential drawback to this approach.