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Drugs Repurposing Using QSAR, Docking and Molecular Dynamics for Possible Inhibitors of the SARS-CoV-2 $M^{pro}$ Protease
| Content Provider | MDPI |
|---|---|
| Author | Andr, és López-Cortés Yunierkis, Pérez-Castillo Tejera, Eduardo Munteanu, Cristian Cabrera-Andrade, Alejandro |
| Copyright Year | 2020 |
| Description | 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 (Mpro) 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 Mpro 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 Mpro enzyme. Five other compounds showed also a negative but small free energy of binding: nikethamide, nifurtimox, rebimastat, apomine and rebastinib. |
| Starting Page | 5172 |
| e-ISSN | 14203049 |
| DOI | 10.3390/molecules25215172 |
| Journal | Molecules |
| Issue Number | 21 |
| Volume Number | 25 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2020-11-06 |
| Access Restriction | Open |
| Subject Keyword | Molecules Medicinal Chemistry Sars-cov-2 Covid-19 Qsar Drugs Repurposing Molecular Dynamics |
| Content Type | Text |
| Resource Type | Article |
