RT Journal Article
T1 In Silico Study of Coumarins and Quinolines Derivatives as Potent Inhibitors of SARS-CoV-2 Main Protease
A1 Yañez, Osvaldo
A1 Osorio, Manuel Isaías
A1 Uriarte Villares, Eugenio
A1 Areche, Carlos
A1 Tiznado, William
A1 Pérez Donoso, José M.
A1 García Beltrán, Olimpio
A1 González Nilo, Fernando
K1 SARS-CoV-2
K1 Coumarins
K1 Quinolines
K1 Protease
K1 Molecular dynamics
AB 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
PB Frontiers
YR 2021
FD 2021
LK http://hdl.handle.net/10347/24686
UL http://hdl.handle.net/10347/24686
LA eng
NO 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
NO The authors express their thanks to Grant RC-FP44842-212-2018 Colombia científica and Universidad de Ibagué and for the financial support of the ANID/PIA/ACT192144. OG-B Thank funding from the Ministry of Science, Technology and Innovation, the Ministry of Education, the Ministry of Industry, Commerce and Tourism, and ICETEX, Programme Ecosistema Científico-Colombia Científica, from the Francisco José de Caldas Fund, Grant RC-FP44842–212-2018
DS Minerva
RD 26 abr 2026