Receptor Interactions of Angiotensin II and Angiotensin Receptor Blockers—Relevance to COVID-19

[img]
Preview
biomolecules-11-00979-v2.pdf - Published Version (2MB) | Preview
Available under license: Creative Commons Attribution

Moore, Graham J, Pires, Jose M, Kelaidonis, Konstantinos, Gadanec, Laura Kate ORCID: 0000-0002-4801-8061, Zulli, Anthony ORCID: 0000-0002-2660-078X, Apostolopoulos, Vasso ORCID: 0000-0001-6788-2771 and Matsoukas, John (2021) Receptor Interactions of Angiotensin II and Angiotensin Receptor Blockers—Relevance to COVID-19. Biomolecules, 11 (7). ISSN 2218-273X

Abstract

Angiotensin II (Ang II) may contain a charge relay system (CRS) involving Tyr/His/ carboxylate, which creates a tyrosinate anion for receptor activation. Energy calculations were carried out to determine the preferred geometry for the CRS in the presence and absence of the Arg guanidino group occupying position 2 of Ang II. These findings suggest that Tyr is preferred over His for bearing the negative charge and that the CRS is stabilized by the guanidino group. Recent crystallography studies provided details of the binding of nonpeptide angiotensin receptor blockers (ARBs) to the Ang II type 1 (AT1) receptor, and these insights were applied to Ang II. A model of binding and receptor activation that explains the surmountable and insurmountable effects of Ang II analogues sarmesin and sarilesin, respectively, was developed and enabled the discovery of a new generation of ARBs called bisartans. Finally, we determined the ability of the bisartan BV6(TFA) to act as a potential ARB, demonstrating similar effects to candesartan, by reducing vasoconstriction of rabbit iliac arteries in response to cumulative doses of Ang II. Recent clinical studies have shown that Ang II receptor blockers have protective effects in hypertensive patients infected with SARS-CoV-2. Therefore, the usage of ARBS to block the AT1 receptor preventing the binding of toxic angiotensin implicated in the storm of cytokines in SARS-CoV-2 is a target treatment and opens new avenues for disease therapy.

Dimensions Badge

Altmetric Badge

Item type Article
URI https://vuir.vu.edu.au/id/eprint/44353
DOI https://doi.org/10.3390/biom11070979
Official URL https://www.mdpi.com/2218-273X/11/7/979
Subjects Current > FOR (2020) Classification > 3201 Cardiovascular medicine and haematology
Current > FOR (2020) Classification > 3204 Immunology
Current > FOR (2020) Classification > 3208 Medical physiology
Current > Division/Research > Institute for Health and Sport
Keywords ACE2, angiotensin II, AT1R, charge relay system, COVID19, EXP3174, SARS-CoV-2, sartans
Citations in Scopus 8 - View on Scopus
Download/View statistics View download statistics for this item

Search Google Scholar

Repository staff login