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

作者信息

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

机构信息

Grupo de Bio-Quimioinformática, Universidad de Las Américas, Quito 170513, Ecuador.

Facultad de Ingeniería y Ciencias Aplicadas, Universidad de Las Américas, Quito 170513, Ecuador.

出版信息

Molecules. 2020 Nov 6;25(21):5172. doi: 10.3390/molecules25215172.


DOI:10.3390/molecules25215172
PMID:33172092
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7664330/
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 (M) 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 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 enzyme. Five other compounds showed also a negative but small free energy of binding: nikethamide, nifurtimox, rebimastat, apomine and rebastinib.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ac2/7664330/cf6b442cec47/molecules-25-05172-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ac2/7664330/40242e16923a/molecules-25-05172-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ac2/7664330/a6e6ac110a8d/molecules-25-05172-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ac2/7664330/cc7f3a26dcbd/molecules-25-05172-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ac2/7664330/cf6b442cec47/molecules-25-05172-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ac2/7664330/40242e16923a/molecules-25-05172-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ac2/7664330/a6e6ac110a8d/molecules-25-05172-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ac2/7664330/cc7f3a26dcbd/molecules-25-05172-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ac2/7664330/cf6b442cec47/molecules-25-05172-g004.jpg

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

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[5]
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[6]
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[7]
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[8]
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Struct Chem. 2022

[9]
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[10]
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本文引用的文献

[1]
Network medicine framework for identifying drug-repurposing opportunities for COVID-19.

Proc Natl Acad Sci U S A. 2021-5-11

[2]
Analyses of Immune System Protein Interactome Network, Single-Cell RNA Sequencing of Human Tissues, and Artificial Neural Networks Reveal Potential Therapeutic Targets for Drug Repurposing Against COVID-19.

Front Pharmacol. 2021-2-26

[3]
SARS-CoV-2 RNA Dependent RNA polymerase (RdRp) - A drug repurposing study.

Heliyon. 2020-7-23

[4]
Clinical, molecular, and epidemiological characterization of the SARS-CoV-2 virus and the Coronavirus Disease 2019 (COVID-19), a comprehensive literature review.

Diagn Microbiol Infect Dis. 2020-5-30

[5]
Current Status of COVID-19 Therapies and Drug Repositioning Applications.

iScience. 2020-7-24

[6]
Bioactivity and Molecular Docking Studies of Derivatives from Cinnamic and Benzoic Acids.

Biomed Res Int. 2020

[7]
In silico prediction of potential inhibitors for the main protease of SARS-CoV-2 using molecular docking and dynamics simulation based drug-repurposing.

J Infect Public Health. 2020-6-16

[8]
Rigorous Free Energy Simulations in Virtual Screening.

J Chem Inf Model. 2020-9-28

[9]
In Silico Evaluation of the Effectivity of Approved Protease Inhibitors against the Main Protease of the Novel SARS-CoV-2 Virus.

Molecules. 2020-5-29

[10]
Unravelling lead antiviral phytochemicals for the inhibition of SARS-CoV-2 M enzyme through in silico approach.

Life Sci. 2020-5-22

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