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Review

ACE2 as a Therapeutic Target for COVID-19; Its Role in Infectious Processes and Regulation by Modulators of the RAAS System

1
Tabula Rasa HealthCare Precision Pharmacotherapy Research & Development Institute, Orlando, FL 32827, USA
2
Faculty of Pharmacy, Université de Montréal, Montreal, QC H3C 3J7, Canada
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(7), 2096; https://doi.org/10.3390/jcm9072096
Received: 11 June 2020 / Revised: 25 June 2020 / Accepted: 2 July 2020 / Published: 3 July 2020
(This article belongs to the Section Pharmacology)
Angiotensin converting enzyme 2 (ACE2) is the recognized host cell receptor responsible for mediating infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ACE2 bound to tissue facilitates infectivity of SARS-CoV-2; thus, one could argue that decreasing ACE2 tissue expression would be beneficial. However, ACE2 catalytic activity towards angiotensin I (Ang I) and II (Ang II) mitigates deleterious effects associated with activation of the renin-angiotensin-aldosterone system (RAAS) on several organs, including a pro-inflammatory status. At the tissue level, SARS-CoV-2 (a) binds to ACE2, leading to its internalization, and (b) favors ACE2 cleavage to form soluble ACE2: these actions result in decreased ACE2 tissue levels. Preserving tissue ACE2 activity while preventing ACE2 shredding is expected to circumvent unrestrained inflammatory response. Concerns have been raised around RAAS modulators and their effects on ACE2 expression or catalytic activity. Various cellular and animal models report conflicting results in various tissues. However, recent data from observational and meta-analysis studies in SARS-CoV-2-infected patients have concluded that RAAS modulators do not increase plasma ACE2 levels or susceptibility to infection and are not associated with more severe diseases. This review presents our current but evolving knowledge of the complex interplay between SARS-CoV-2 infection, ACE2 levels, modulators of RAAS activity and the effects of RAAS modulators on ACE2 expression. View Full-Text
Keywords: ACE2; SARS-CoV-2; renin-angiotensin-aldosterone system; angiotensin II converting enzyme inhibitors; angiotensin II type 1 receptor blockers; pneumonia ACE2; SARS-CoV-2; renin-angiotensin-aldosterone system; angiotensin II converting enzyme inhibitors; angiotensin II type 1 receptor blockers; pneumonia
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MDPI and ACS Style

Michaud, V.; Deodhar, M.; Arwood, M.; Al Rihani, S.B.; Dow, P.; Turgeon, J. ACE2 as a Therapeutic Target for COVID-19; Its Role in Infectious Processes and Regulation by Modulators of the RAAS System. J. Clin. Med. 2020, 9, 2096. https://doi.org/10.3390/jcm9072096

AMA Style

Michaud V, Deodhar M, Arwood M, Al Rihani SB, Dow P, Turgeon J. ACE2 as a Therapeutic Target for COVID-19; Its Role in Infectious Processes and Regulation by Modulators of the RAAS System. Journal of Clinical Medicine. 2020; 9(7):2096. https://doi.org/10.3390/jcm9072096

Chicago/Turabian Style

Michaud, Veronique, Malavika Deodhar, Meghan Arwood, Sweilem B. Al Rihani, Pamela Dow, and Jacques Turgeon. 2020. "ACE2 as a Therapeutic Target for COVID-19; Its Role in Infectious Processes and Regulation by Modulators of the RAAS System" Journal of Clinical Medicine 9, no. 7: 2096. https://doi.org/10.3390/jcm9072096

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