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- Title
Drugs Repurposing Using QSAR, Docking and Molecular Dynamics for Possible Inhibitors of the SARS-CoV-2 M pro Protease.
- Authors
Tejera, Eduardo; Munteanu, Cristian R.; López-Cortés, Andrés; Cabrera-Andrade, Alejandro; Pérez-Castillo, Yunierkis; Toropova, Alla P.; Gauld, James W.
- Abstract
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.
- Subjects
WUHAN (China); COVID-19; SARS-CoV-2; MOLECULAR dynamics; MOLECULAR docking; COVID-19 pandemic; PROTEOLYTIC enzymes
- Publication
Molecules, 2020, Vol 25, Issue 21, p5172
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules25215172