Insights into the actions of angiotensin-1 receptor (AT1R) inverse agonists: Perspectives and implications in COVID-19 treatment

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Luana Heimfarth
Mario Adriano dos Santos
José Augusto Barreto-Filho
André Barreto
Fabricio Macedo
Adriano Araújo
Paulo Martins-Filho
Marcus Scotti
Luciana Scotti
Lucindo Quintans-Júnior

Abstract

New coronavirus SARS-CoV-2 (COVID-19) has caused chaos in health care systems. Clinical manifestations of COVID-19 are variable, with a complex pathophysiology and as yet no specific treatment. It has been suggested that the renin-angiotensin-aldosterone system has a possible role in the severity of cases and the number of deaths. Our hypothesis is that drugs with inverse agonist effects to the angiotensin-1 receptor can be promising tools in the management of patients with COVID-19, possibly avoiding complications and the poor evolution in some cases. Any risk factors first need to be identified, and the most appropriate time to administer the drugs during the course of the infection also needs to be established. Several angiotensin receptor blockers (ARB) have a favorable profile and are important candidates for the treatment of COVID-19. In this review we discussed a set of compounds with favorable profile for COVID-19 treatment, including azilsartan, candesartan, eprosartan, EXP3174, olmesartan, telmisartan, and valsartan. They are effective as inverse agonists and could reduce the “cytokine storm” and reducing oxidative stress. As COVID-19 disease has several evolution patterns, the effectiveness of ARB therapy would be related to infection "timing", patient risk factors, previous use of ARBs, and the specific molecular effects of an ARB. However, controlled studies are needed to identify whether ARBs are beneficial in the treatment of patients with COVID-19.

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How to Cite
Heimfarth, L., dos Santos, M. A., Barreto-Filho , J. A., Barreto, A., Macedo, F., Araújo, A., Martins-Filho, P., Scotti, M., Scotti, L., & Quintans-Júnior, L. . (2021). Insights into the actions of angiotensin-1 receptor (AT1R) inverse agonists: Perspectives and implications in COVID-19 treatment. EXCLI Journal, 20, 252-275. https://doi.org/10.17179/excli2021-3412
Section
Review articles
Author Biography

Lucindo Quintans-Júnior, Laboratory of Neuroscience and Pharmacological Assays (LANEF), Department of Physiology, Federal University of Sergipe-UFS, Av. Marechal Rondom, s/n, São Cristóvão, Sergipe, Brazil. Zip Code: 49.100-000. Tel.: +55-79-21056645; Fax: +55-79-3212-6640. E-mail: lucindo@academico.edu.br; lucindojr@gmail.com

Prof Lucindo Quintans Júnior

Federal University of Sergipe/Brazil

Member of Brazilian Association of Pharmaceutical Sciences (ABCF)

Web of Science ResearcherID: A-2434-2012

Scopus Author ID: 6506141950

ORCID: 0000-0001-5155-938X 

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