In Silico Study of Coumarins and Quinolines Derivatives as Potent Inhibitors of SARS-CoV-2 Main Protease

dc.creatorYa?ez, Osvaldo
dc.creatorOsorio, Manuel Isa?as
dc.creatorUriarte, Eugenio
dc.creatorAreche, Carlos
dc.creatorTiznado, William
dc.creatorP?rez-Donoso, Jos? M.
dc.creatorGarc?a-Beltr?n, Olimpo
dc.creatorGonz?lez-Nilo, Fernando
dc.date2021-07-23T20:55:07Z
dc.date2021-07-23T20:55:07Z
dc.date2021-02-08
dc.date.accessioned2023-08-31T19:21:51Z
dc.date.available2023-08-31T19:21:51Z
dc.identifierYa?ez O, Osorio MI, Uriarte E, Areche C, Tiznado W, Perez-donoso JM, Garc?a O and Gonz?lez FD(2020) In Silico Study of Coumarins and Quinolines Derivatives as Potent Inhibitors of SARS-CoV-2 Main Protease. Front. Chem. 8:1273. doi:10.3389/fchem.2020.595097
dc.identifier2296-2646
dc.identifierhttps://www.frontiersin.org/articles/10.3389/fchem.2020.595097/full
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8557385
dc.descriptionThe 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.
dc.descriptionUniversidad de Ibagu?
dc.languageen
dc.publisherFrontiers in Chemistry
dc.subjectCoumarins
dc.subjectMolecular dynamics
dc.subjectProtease
dc.subjectQuinolines
dc.subjectSARS-CoV-2
dc.titleIn Silico Study of Coumarins and Quinolines Derivatives as Potent Inhibitors of SARS-CoV-2 Main Protease
dc.typeArticle


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