Wuhan, China was the epicenter of the first zoonotic transmission of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) in December 2019 and it is the causative agent of the novel human coronavirus disease 2019 (COVID-19). Almost from the beginning of the COVID-19 outbreak several attempts were made to predict possible drugs capable of inhibiting the virus replication. In the present work a drug repurposing study is performed to identify potential SARS-CoV-2 protease inhibitors. We created a Quantitative Structure–Activity Relationship (QSAR) model based on a machine learning strategy using hundreds of inhibitor molecules of the main protease (M pro ) of the SARS-CoV coronavirus. The QSAR model was used for virtual screening of a large list of drugs from the DrugBank database. The best 20 candidates were then evaluated in-silico against the M pro of SARS-CoV-2 by using docking and molecular dynamics analyses. Docking was done by using the Gold software, and the free energies of binding were predicted with the MM-PBSA method as implemented in AMBER. Our results indicate that levothyroxine, amobarbital and ABP-700 are the best potential inhibitors of the SARS-CoV-2 virus through their binding to the M pro enzyme. Five other compounds showed also a negative but small free energy of binding: nikethamide, nifurtimox, rebimastat, apomine and rebastinib.
【저자키워드】 COVID-19, SARS-CoV-2, molecular dynamics, QSAR, drugs repurposing, 【초록키워드】 coronavirus disease, Coronavirus disease 2019, coronavirus, SARS-CoV, SARS-CoV-2 virus, Virtual screening, drug, docking, molecular dynamics, protease, inhibitors, free energy, COVID-19 outbreak, gold, clade, virus replication, molecular, respiratory, in-silico, inhibitor, predict, binding, best, causative agent, quantitative structure–activity relationship, amobarbital, nikethamide, apomine, free energies, acute respiratory syndrome, rebimastat, nifurtimox, acute respiratory syndrome coronavirus, enzyme, epicenter, SARS-CoV-2 protease, M pro, candidate, zoonotic transmission, ABP-700, DrugBank database, levothyroxine, rebastinib, relationship, Wuhan, China, human coronavirus, predicted, identify, performed, was used, evaluated, analyses, inhibiting, was done, other compound, the SARS-CoV-2 virus, 【제목키워드】 Dynamics, repurposing, drug, molecular dynamics, the SARS-CoV-2,