In Silico Study of Coumarins and Quinolines Derivatives as Potent Inhibitors of SARS-CoV-2 Main Protease
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Fecha
2021-02
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Facultad/escuela
Idioma
en
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Frontiers Media S.A.
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Licencia CC
AtribuciĆ³n 4.0 Internacional (CC BY 4.0)
Licencia CC
https://creativecommons.org/licenses/by/4.0/deed.es
Resumen
The pandemic that started in Wuhan (China) in 2019 has caused a large number of deaths, and infected people around the world due to the absence of effective therapy against coronavirus 2 of the severe acute respiratory syndrome (SARS-CoV-2). Viral maturation requires the activity of the main viral protease (Mpro), so its inhibition stops the progress of the disease. To evaluate possible inhibitors, a computational model of the SARS-CoV-2 enzyme Mpro was constructed in complex with 26 synthetic ligands derived from coumarins and quinolines. Analysis of simulations of molecular dynamics and molecular docking of the models show a high affinity for the enzyme (āEbinding between ā5.1 and 7.1 kcal molā1). The six compounds with the highest affinity show Kd between 6.26 Ć 10ā6 and 17.2 Ć 10ā6, with binding affinity between ā20 and ā25 kcal molā1, with ligand efficiency less than 0.3 associated with possible inhibitory candidates. In addition to the high affinity of these compounds for SARS-CoV-2 Mpro, low toxicity is expected considering the Lipinski, Veber and Pfizer rules. Therefore, this novel study provides candidate inhibitors that would allow experimental studies which can lead to the development of new treatments for SARS-CoV-2. Ā© Copyright Ā© 2021 YaƱez, Osorio, Uriarte, Areche, Tiznado, Perez-Donoso, GarcĆa-BeltrĆ”n and GonzĆ”lez-Nilo.
Notas
IndexaciĆ³n: Scopus
Palabras clave
Coumarins, Molecular dynamics, Protease, Quinolines, SARS-CoV-2
CitaciĆ³n
Frontiers in Chemistry Volume 88 February 2021 Article number 595097
DOI
10.3389/fchem.2020.595097