Abstract
Blocking the main replicating enzyme, 3 Chymotrypsin-like protease (3CL pro ) is the most promising drug development strategy against the SARS-CoV-2 virus, responsible for the current COVID-19 pandemic. In the present work, 9101 drugs obtained from the drug bank database were screened against SARS-CoV-2 3CL pro prosing deep learning, molecular docking, and molecular dynamics simulation techniques. In the initial stage, 500 drug-screened by deep learning regression model and subjected to molecular docking that resulted in 10 screened compounds with strong binding affinity. Further, five compounds were checked for their binding potential by analyzing molecular dynamics simulation for 100 ns at 300 K. In the final stage, two compounds {4-[(2s,4e)-2-(1,3-Benzothiazol-2-Yl)-2-(1h-1,2,3-Benzotriazol-1-Yl)-5-Phenylpent-4-Enyl]Phenyl}(Difluoro)Methylphosphonic Acid and 1-(3-(2,4-dimethylthiazol-5-yl)-4-oxo-2,4-dihydroindeno[1,2-c]pyrazol-5-yl)-3-(4-methylpiperazin-1-yl)urea were screened as potential hits by analyzing several parameters like RMSD, Rg, RMSF, MMPBSA, and SASA. Thus, our study suggests two potential drugs that can be tested in the experimental conditions to evaluate the efficacy against SARS-CoV-2. Further, such drugs could be modified to develop more potent drugs against COVID-19.
Keywords: 3CLpro; COVID-19; Deep learning; Drug bank database; Drug repurposing; Molecular dynamics.
【저자키워드】 COVID-19, Drug repurposing, deep learning, 3CLpro, molecular dynamics., Drug bank database, 【초록키워드】 Drug repurposing, SARS-CoV-2, Efficacy, COVID-19 pandemic, molecular docking, SARS-CoV-2 virus, drug, 3CL pro, molecular dynamics, database, binding affinity, Molecular dynamics simulation, Regression model, binding, RMSD, RMSF, Chymotrypsin-like protease, urea, initial stage, enzyme, Compound, Final, acid, parameter, blocking, FIVE, deep, Drug Bank, Methylphosphonic acid, initial, responsible, tested, develop, evaluate, screened, condition, checked, the SARS-CoV-2 virus, 【제목키워드】 SARS-CoV-2, 3CL pro, protease, Compound,