A hypothesis for pathobiology and treatment of COVID-19: The centrality of ACE1/ACE2 imbalance.
Br J Pharmacol
; 177(21): 4825-4844, 2020 11.
Article
in English
| MEDLINE | ID: covidwho-998826
ABSTRACT
Angiotensin Converting Enzyme2 is the cell surface binding site for the coronavirus SARS-CoV-2, which causes COVID-19. We propose that an imbalance in the action of ACE1- and ACE2-derived peptides, thereby enhancing angiotensin II (Ang II) signalling is 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 ANG II. This hypothesis suggests several approaches to treat COVID-19 by restoring ACE1/ACE2 balance (a) AT receptor antagonists; (b) ACE1 inhibitors (ACEIs); (iii) agonists of receptors activated by ACE2-derived peptides (e.g. Ang (1-7), which activates MAS1); (d) 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 AT antagonists and ACEIs can be rapidly repurposed to test their efficacy in treating COVID-19. LINKED ARTICLES This article is part of a themed issue on The Pharmacology of COVID-19. To view the other articles in this section visit http//onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Pneumonia, Viral
/
Coronavirus Infections
/
Betacoronavirus
Type of study:
Prognostic study
Limits:
Animals
/
Humans
Language:
English
Journal:
Br J Pharmacol
Year:
2020
Document Type:
Article
Affiliation country:
Bph.15082
Similar
MEDLINE
...
LILACS
LIS