Journal
MOLECULES
Volume 25, Issue 21, Pages -Publisher
MDPI
DOI: 10.3390/molecules25215172
Keywords
SARS-CoV-2; COVID-19; QSAR; drugs repurposing; molecular dynamics
Funding
- Universidad de LasAmericas, Quito, Ecuador [BIO.TPA.20.03]
- Collaborative Project in Genomic Data Integration (CICLOGEN) - Carlos III Health Institute from the Spanish National plan for Scientific and Technical Research and Innovation 2013-2016 [PI17/01826]
- European Regional Development Funds (FEDER)-A way to build Europe
- Consolidation and Structuring of Competitive Research Units-Competitive Reference Groups - Ministry of Education, University and Vocational Training of the Xunta de Galicia [ED431C 2018/49]
- EU FEDER funds
- Universidad de Las Americas, Quito, Ecuador
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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.
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