In Silico Study towards Repositioning of FDA-Approved Drug Candidates for Anticoronaviral Therapy: Molecular Docking, Molecular Dynamics and Binding Free Energy Calculations
| Autor: | Wesam S. Qayed, Rafaela S. Ferreira, José Rogério A. Silva |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
Digoxin
SARS-CoV-2 Organic Chemistry Drug Repositioning Pharmaceutical Science COVID-19 Molecular Dynamics Simulation RNA-Dependent RNA Polymerase Antiviral Agents Analytical Chemistry Molecular Docking Simulation Cysteine Endopeptidases Digitoxin Chemistry (miscellaneous) Proscillaridin Drug Discovery Papain Molecular Medicine Humans Niclosamide anti-COVID-19 drug repositioning molecular docking molecular dynamic simulations binding free energy Physical and Theoretical Chemistry Ouabain |
| Zdroj: | Molecules; Volume 27; Issue 18; Pages: 5988 |
| ISSN: | 1420-3049 |
| Popis: | The SARS-CoV-2 targets were evaluated for a set of FDA-approved drugs using a combination of drug repositioning and rigorous computational modeling methodologies such as molecular docking and molecular dynamics (MD) simulations followed by binding free energy calculations. Six FDA-approved drugs including, Ouabain, Digitoxin, Digoxin, Proscillaridin, Salinomycin and Niclosamide with promising anti-SARS-CoV-2 activity were screened in silico against four SARS-CoV-2 proteins—papain-like protease (PLpro), RNA-dependent RNA polymerase (RdRp), SARS-CoV-2 main protease (Mpro), and adaptor-associated kinase 1 (AAK1)—in an attempt to define their promising targets. The applied computational techniques suggest that all the tested drugs exhibited excellent binding patterns with higher scores and stable complexes compared to the native protein cocrystallized inhibitors. Ouabain was suggested to act as a dual inhibitor for both PLpro and Mpro enzymes, while Digitoxin bonded perfectly to RdRp. In addition, Salinomycin targeted PLpro. Particularly, Niclosamide was found to target AAK1 with greater affinity compared to the reference drug. Our study provides comprehensive molecular-level insights for identifying or designing novel anti-COVID-19 drugs. |
| Databáze: | OpenAIRE |
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