In Silico Study of Coumarins and Quinolines Derivatives as Potent Inhibitors of SARS-CoV-2 Main Protease
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http://hdl.handle.net/10347/24686
Título: | In Silico Study of Coumarins and Quinolines Derivatives as Potent Inhibitors of SARS-CoV-2 Main Protease
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Autor/a: | Yañez, Osvaldo
Osorio, Manuel Isaías
Uriarte Villares, Eugenio
Areche, Carlos
Tiznado, William
Pérez Donoso, José M.
García Beltrán, Olimpio
González Nilo, Fernando
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Centro/Departamento: | Universidade de Santiago de Compostela. Departamento de Química Orgánica
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Palabras chave: | SARS-CoV-2 | Coumarins | Quinolines | Protease | Molecular dynamics | |
Data: | 2021
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Editor: | Frontiers
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Cita bibliográfica: | Yañez O, Osorio MI, Uriarte E, Areche C, Tiznado W, Pérez-Donoso JM, García-Beltrán O and González-Nilo F (2021) In Silico Study of Coumarins and Quinolines Derivatives as Potent Inhibitors of SARS-CoV-2 Main Protease. Front. Chem. 8:595097. doi: 10.3389/fchem.2020.595097
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Resumo: | 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 (∆Ebinding between −5.1 and 7.1 kcal mol−1). The six compounds with the highest affinity show Kd between 6.26 × 10–6 and 17.2 × 10–6, with binding affinity between −20 and −25 kcal mol−1, 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 |
Versión do editor: | https://doi.org/10.3389/fchem.2020.595097 |
URI: | http://hdl.handle.net/10347/24686
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DOI: | 10.3389/fchem.2020.595097 |
E-ISSN: | 2296-2646
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Dereitos: | Copyright © 2021 Yañez, Osorio, Uriarte, Areche, Tiznado, Perez-Donoso, García-Beltrán and González-Nilo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms Atribución 4.0 Internacional
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