Binding and inhibitory effect of ravidasvir on 3CLpro of SARS-CoV-2: a molecular docking, molecular dynamics and MM/PBSA approach
| Autoři | |
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| Rok publikování | 2022 |
| Druh | Článek v odborném periodiku |
| Časopis / Zdroj | Journal of Biomolecular Structure and Dynamics |
| Fakulta / Pracoviště MU | |
| Citace | |
| www | https://www.tandfonline.com/doi/full/10.1080/07391102.2021.1896388 |
| Doi | http://dx.doi.org/10.1080/07391102.2021.1896388 |
| Klíčová slova | 3CLpro; MM/PBSA; SARS-CoV-2; molecular docking; molecular dynamics simulation; principal component analysis |
| Popis | Drug repurposing requires a limited resource, cost-effective and faster method to combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, this in silico studies attempts to identify the drug-likeness properties of ravidasvir, an II/III phase clinical trial chronic hepatitis C drug against 3-Chymotrypsin-like protease (3CLpro) of SARS-CoV-2 to combat the ongoing coronavirus disease 2019 (COVID-19) pandemic. This protease is predominantly involved in virus replication cycle; hence it is considered as a potent drug target. The molecular docking results showed that ravidasvir was found to be potent inhibitors of 3CLpro with scoring function based binding energy is -26.7kJ/mol. Further dynamic behaviour of apo form and complex form of ravidasvir with 3CLpro were studied using molecular dynamics (MD) simulations over 500ns each, total 2s time scale. The motion of the protein was studied using principal component analysis of the MD simulation trajectories. The binding free energy calculated using MM/PBSA method from the MD simulation trajectory was -190.3±70.2kJ/mol and -106.0±26.7kJ/mol for GROMOS96 54A7 and AMBER99SB-ILDN force field, respectively. This in silico studies suggesting ravidasvir might be a potential lead molecule against SARS-CoV-2 for further optimization and drug development to combat the life-threatening COVID-19 pandemic.Communicated by Ramaswamy H. Sarma. |
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