Drugs Repurposing Using QSAR, Docking and Molecular Dynamics for Possible Inhibitors of the SARS-CoV-2 Mpro Protease

Eduardo Tejera, Cristian R. Munteanu, Andrés López-Cortés, Alejandro Cabrera-Andrade, Yunierkis Pérez-Castillo

10.3390/molecules25215172

Research curated

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.

Source: PubMed

Related molecules

Name	Synonyms	Genes
Levothyroxine
Amobarbital
ABP-700
Nikethamide
Nifurtimox
Rebimastat
Apomine
Rebastinib
3C-like protease	3CLpro, Mpro, SARS coronavirus main peptidase, 3CLpro-SARS-CoV-2	rep, ORF1a-1b

Related interactions

Target	Drug	Type	Result
3C-like protease	Levothyroxine	Computational	positive
3C-like protease	Amobarbital	Computational	positive
3C-like protease	ABP-700	Computational	positive
3C-like protease	Nikethamide	Computational	positive
3C-like protease	Nifurtimox	Computational	positive
3C-like protease	Rebimastat	Computational	positive
3C-like protease	Apomine	Computational	positive