Molecular features of non-selective small molecule antagonists of the Bradykinin receptors
Angiotensin converting enzyme 2 (ACE2) downregulation is a key negative factor for the severity of lung edema and acute lung failure observed in patients infected with SARS-CoV-2. ACE2 downregulation affects the levels of diverse peptide mediators of the renin-agiotensin-aldestosterone and kallikrei...
| Autores: | , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2020 |
| País: | España |
| Institución: | Universitat Politècnica de Catalunya (UPC) |
| Repositorio: | UPCommons. Portal del coneixement obert de la UPC |
| Idioma: | inglés |
| OAI Identifier: | oai:upcommons.upc.edu:2117/334784 |
| Acceso en línea: | https://hdl.handle.net/2117/334784 https://dx.doi.org/10.3390/ph13090259 |
| Access Level: | acceso abierto |
| Palabra clave: | COVID-19 (Disease) Bradykinin receptors Bradykinin pharmacophore Non-peptide bradykinin antagonists Bradykinin repurposing Covid-19 therapy COVID-19 (Malaltia) Molècules Àrees temàtiques de la UPC::Enginyeria química |
| Sumario: | Angiotensin converting enzyme 2 (ACE2) downregulation is a key negative factor for the severity of lung edema and acute lung failure observed in patients infected with SARS-CoV-2. ACE2 downregulation affects the levels of diverse peptide mediators of the renin-agiotensin-aldestosterone and kallikrein-kinin systems, compromising vascular hemostasis. Increasing evidence suggests that the inflammatory response observed in covid-19 patients is initiated by the action of kinins on the bradykinin receptors. Accordingly, the use of bradykinin antagonists should be considered as a strategy for therapeutic intervention against covid-19 illness progression. Presently, icatibant is the only bradykinin antagonist drug approved. In the present report, we investigated the molecular features characterizing non-selective antagonists targeting the bradykinin receptors and carried out a in silico screening of approved drugs, aimed at the identification of compounds with a non-selective bradykinin antagonist profile that can be evaluated for drug repurposing. The study permitted to identify eight compounds as prospective non-selective antagonists of the bradykinin receptors, including raloxifene; sildenafil; cefepime; cefpirome; imatinib; ponatinib; abemaciclib and entrectinib. |
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