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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.
Afiliação
  • Moore GJ; Pepmetics Inc., 772 Murphy Place, Victoria, BC V8Y 3H4, Canada.
  • Pires JM; Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada.
  • Kelaidonis K; Department of Physics, Federal University of Espirito, Santo, Vitoria 29075-910, Brazil.
  • Gadanec LK; NewDrug, Patras Science Park, 26500 Patras, Greece.
  • Zulli A; Institute for Health and Sport, Victoria University, Melbourne, VIC 3030, Australia.
  • Apostolopoulos V; Institute for Health and Sport, Victoria University, Melbourne, VIC 3030, Australia.
  • Matsoukas JM; Institute for Health and Sport, Victoria University, Melbourne, VIC 3030, Australia.
Biomolecules ; 11(7)2021 07 03.
Article em En | MEDLINE | ID: mdl-34356603
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Angiotensina II / Receptor Tipo 1 de Angiotensina / Descoberta de Drogas / Antagonistas de Receptores de Angiotensina / Tratamento Farmacológico da COVID-19 Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Revista: Biomolecules Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Canadá País de publicação: Suíça

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Angiotensina II / Receptor Tipo 1 de Angiotensina / Descoberta de Drogas / Antagonistas de Receptores de Angiotensina / Tratamento Farmacológico da COVID-19 Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Revista: Biomolecules Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Canadá País de publicação: Suíça