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Receptor Interactions of Angiotensin II and Angiotensin Receptor Blockers—Relevance to COVID-19
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 occupyi...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301908/ https://www.ncbi.nlm.nih.gov/pubmed/34356603 http://dx.doi.org/10.3390/biom11070979 |
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author | Moore, Graham J. Pires, Jose M. Kelaidonis, Konstantinos Gadanec, Laura Kate Zulli, Anthony Apostolopoulos, Vasso Matsoukas, John M. |
author_facet | Moore, Graham J. Pires, Jose M. Kelaidonis, Konstantinos Gadanec, Laura Kate Zulli, Anthony Apostolopoulos, Vasso Matsoukas, John M. |
author_sort | Moore, Graham J. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8301908 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-83019082021-07-24 Receptor Interactions of Angiotensin II and Angiotensin Receptor Blockers—Relevance to COVID-19 Moore, Graham J. Pires, Jose M. Kelaidonis, Konstantinos Gadanec, Laura Kate Zulli, Anthony Apostolopoulos, Vasso Matsoukas, John M. Biomolecules Article 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. MDPI 2021-07-03 /pmc/articles/PMC8301908/ /pubmed/34356603 http://dx.doi.org/10.3390/biom11070979 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Moore, Graham J. Pires, Jose M. Kelaidonis, Konstantinos Gadanec, Laura Kate Zulli, Anthony Apostolopoulos, Vasso Matsoukas, John M. Receptor Interactions of Angiotensin II and Angiotensin Receptor Blockers—Relevance to COVID-19 |
title | Receptor Interactions of Angiotensin II and Angiotensin Receptor Blockers—Relevance to COVID-19 |
title_full | Receptor Interactions of Angiotensin II and Angiotensin Receptor Blockers—Relevance to COVID-19 |
title_fullStr | Receptor Interactions of Angiotensin II and Angiotensin Receptor Blockers—Relevance to COVID-19 |
title_full_unstemmed | Receptor Interactions of Angiotensin II and Angiotensin Receptor Blockers—Relevance to COVID-19 |
title_short | Receptor Interactions of Angiotensin II and Angiotensin Receptor Blockers—Relevance to COVID-19 |
title_sort | receptor interactions of angiotensin ii and angiotensin receptor blockers—relevance to covid-19 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301908/ https://www.ncbi.nlm.nih.gov/pubmed/34356603 http://dx.doi.org/10.3390/biom11070979 |
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