In silico evaluation of flavonoids as potential inhibitors of SARS-CoV-2 main nonstructural proteins (Nsps)-amentoflavone as a multitarget candidate.

Autor: Portilla-Martínez A; Sección de Posgrado, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis Y Diaz Mirón S/N, Col Santo Tomás, 11340, Mexico City, Mexico., Ortiz-Flores M; Sección de Posgrado, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis Y Diaz Mirón S/N, Col Santo Tomás, 11340, Mexico City, Mexico., Hidalgo I; Laboratorio de Investigación en Inmunología Y Salud Pública, Facultad de Estudios Superiores Cuautitlán, Unidad de Investigación Multidisciplinaria Universidad Nacional Autónoma de México, Estado de México, Mexico City, Mexico., Gonzalez-Ruiz C; Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Mexico City, Mexico., Meaney E; Sección de Posgrado, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis Y Diaz Mirón S/N, Col Santo Tomás, 11340, Mexico City, Mexico., Ceballos G; Sección de Posgrado, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis Y Diaz Mirón S/N, Col Santo Tomás, 11340, Mexico City, Mexico., Nájera N; Sección de Posgrado, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis Y Diaz Mirón S/N, Col Santo Tomás, 11340, Mexico City, Mexico. nnajerag@ipn.mx.
Jazyk: angličtina
Zdroj: Journal of molecular modeling [J Mol Model] 2022 Nov 29; Vol. 28 (12), pp. 404. Date of Electronic Publication: 2022 Nov 29.
DOI: 10.1007/s00894-022-05391-6
Abstrakt: Despite the development of vaccines against COVID-19 disease and the multiple efforts to find efficient drugs as treatment for this virus, there are too many social, political, economic, and health inconveniences to incorporate a fully accessible plan of prevention and therapy against SARS-CoV-2. In this sense, it is necessary to find nutraceutical/pharmaceutical drugs as possible COVID-19 preventives/treatments. Based on their beneficial effects, flavonoids are one of the most promising compounds. Therefore, using virtual screening, 478 flavonoids obtained from the KEGG database were evaluated against non-structural proteins Nsp1, Nsp3, Nsp5, Nsp12, and Nsp15, which are essential for the virus-host cell infection, searching for possible multitarget flavonoids. Amentoflavone, a biflavonoid found mainly in Ginkgo biloba, Lobelia chinensis, and Byrsonima intermedia, can interact and bind with the five proteins, suggesting its potential as a multitarget inhibitor. Molecular docking calculations and structural analysis (RMSD, number of H bonds, and clustering) performed from molecular dynamics simulations of the amentoflavone-protein complex support this potential. The results shown here are theoretical evidence of the probable multitarget inhibition of non-structural proteins of SARS-CoV-2 by amentoflavone, which has wide availability, low cost, no side effects, and long history of use. These results are solid evidence for future in vitro and in vivo experiments aiming to validate amentoflavone as an inhibitor of the Nsp1, 3, 5, 12, and 15 of SARS-CoV-2.
(© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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