Molecular docking, molecular dynamics simulation, and ADMET analysis of levamisole derivatives against the SARS-CoV-2 main protease (M Pro )

Molecular docking, molecular dynamics simulation, and ADMET analysis of levamisole derivatives against the SARS-CoV-2 main protease (M Pro ) Khalil EL Khatabi Molecular Chemistry and Natural Substances Laboratory, Faculty of Science, Moulay Ismail University of Meknes, Morocco http://orcid.org/0000-0001-8669-9657 Ilham Aanouz Molecular Chemistry and Natural Substances Laboratory, Faculty of Science, Moulay Ismail University of Meknes, Morocco Marwa Alaqarbeh National Agricultural Research Center, Al‑Baqa 19381, Jordan Mohammed Aziz Ajana Molecular Chemistry and Natural Substances Laboratory, Faculty of Science, Moulay Ismail University of Meknes, Morocco Tahar Lakhlifi Molecular Chemistry and Natural Substances Laboratory, Faculty of Science, Moulay Ismail University of Meknes, Morocco Mohammed Bouachrine Molecular Chemistry and Natural Substances Laboratory, Faculty of Science, Moulay Ismail University of Meknes, Morocco EST Khenifra, Sultan MoulaySliman University, Benimellal, Morocco http://orcid.org/0000-0002-8901-047X

Introduction: The new species of coronaviruses (CoVs), SARS-CoV-2, was reported as responsible for an outbreak of respiratory disease. Scientists and researchers are endeavoring to develop new approaches for the effective treatment against of the COVID-19 disease. There are no finally targeted antiviral agents able to inhibit the SARS-CoV-2 at present. Therefore, it is of interest to investigate the potential uses of levamisole derivatives, which are reported to be antiviral agents targeting the influenza virus. Methods: In the present study, 12 selected levamisole derivatives containing imidazo[2,1-b]thiazole were subjected to molecular docking in order to explore the binding mechanisms between these derivatives and the SARS-CoV-2 Mpro (PDB: 7BQY). The levamisole derivatives were evaluated for in silico ADMET properties for wet-lab applicability. Further, the stability of the best-docked complex was checked using molecular dynamics (MD) simulation at 20 ns. Results: Levamisole derivatives and especially molecule N°6 showed more promising docking results, presenting favorable binding interactions as well as better docking energy compared to chloroquine and mefloquine. The results of ADMET prediction and MD simulation support the potential of the molecule N°6 to be further developed as a novel inhibitor able to stop the newly emerged SARS-CoV-2. Conclusion: This research provided an effective first line in the rapid discovery of drug leads against the novel CoV (SARS-CoV-2).
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