Receptor Interactions of Angiotensin II and Angiotensin Receptor Blockers-Relevance to COVID-19
| Autor: | Anthony Zulli, José Maria Pires, John Matsoukas, Graham J. Moore, Konstantinos Kelaidonis, Laura Kate Gadanec, Vasso Apostolopoulos |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Models Molecular COVID19 EXP3174 ACE2 Pharmacology Crystallography X-Ray Microbiology Biochemistry AT1R Receptor Angiotensin Type 1 Article 03 medical and health sciences Angiotensin Receptor Antagonists 0302 clinical medicine Renin–angiotensin system Drug Discovery medicine Animals Humans Receptor Molecular Biology 030304 developmental biology 0303 health sciences Angiotensin II receptor type 1 Chemistry Drug discovery SARS-CoV-2 Angiotensin II COVID-19 sartans QR1-502 COVID-19 Drug Treatment Candesartan Vasoconstriction 030220 oncology & carcinogenesis charge relay system Hypertension Angiotensin Receptor Blockers Rabbits medicine.symptom hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | Biomolecules Biomolecules, Vol 11, Iss 979, p 979 (2021) Volume 11 Issue 7 |
| ISSN: | 2218-273X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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