loading page

A hypothesis for pathobiology and treatment of COVID-19: the centrality of ACE1/ACE2 imbalance
  • Krishna Sriram,
  • Paul Insel
Krishna Sriram
University of California San Diego

Corresponding Author:[email protected]

Author Profile
Paul Insel
Author Profile


Angiotensin converting enzyme-2 (ACE2) is the receptor for the coronavirus SARS-CoV-2, which causes COVID-19. We propose the following hypothesis: Imbalance in the action of ACE1- and ACE2-derived peptides, thereby enhancing Angiotensin-II (ANG II) signaling, a primary driver of COVID-19 pathobiology. ACE1/ACE2 imbalance occurs due to the binding of SARS-CoV-2 to ACE2, reducing ACE2-mediated conversion of ANG II to ANG peptides that counteract pathophysiological effects of ACE1-generated ANGII. This hypothesis suggests several approaches to treat COVID-19 by restoring ACE1/ACE2 balance: 1) ANG II receptor blockers (ARBs); 2) ACE1 inhibitors (ACEIs); 3) Agonists of receptors activated by ACE2-derived peptides [e.g., ANG (1-7), which activates MAS1]; 4) Recombinant human ACE2 or ACE2 peptides as decoys for the virus. Reducing ACE1/ACE2 imbalance is predicted to blunt COVID-19-associated morbidity and mortality, especially in vulnerable patients. Importantly, approved ARBs and ACEIs can be rapidly repurposed to test their efficacy in treating COVID-19.
11 Apr 2020Submitted to British Journal of Pharmacology
13 Apr 2020Submission Checks Completed
13 Apr 2020Assigned to Editor
13 Apr 2020Reviewer(s) Assigned
15 Apr 2020Editorial Decision: Revise Minor
17 Apr 20201st Revision Received
20 Apr 2020Submission Checks Completed
20 Apr 2020Assigned to Editor
20 Apr 2020Reviewer(s) Assigned
20 Apr 2020Editorial Decision: Accept