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

Abstract

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).

The potential immunomodulatory effect of levamisole in humans and farm animals

“…However, during therapy, there was a nonsignificant alteration in dyspnea, cough, diarrhea, nausea, vomiting, sore throat, hyposmia, dysgeusia, and anorexia compared to the control group [99] . Interestingly, levamisole derivatives could be used as the main drug for COVID-19 treatment because they contain the molecule N°6 structure in levamisole, which could be further developed to stop the COVID-19 pandemic [100] . Altogether, it can be concluded that levamisole and its derivatives can be used in the future as antiviral drugs.…”

Discover the Medication Potential of Algerian Medicinal Plants Against Sars-Cov-2 Main Protease (Mpro): Molecular Docking, Molecular Dynamic Simulation, and ADMET Analysis

“…Molecular docking was used to study the interaction of active compounds of Algerian plants with the Sars-Cov-2 protease target [ 11 , 12 ]. The target proteins are major (6WTT and 6LU7) proteases of the Sars-CoV-2 virus.…”

Molecular dynamics studies reveal structural and functional features of the SARS‐CoV‐2 spike protein

“…Other attempts against MPro were done [ 130 , 131 , 132 , 133 ] but require further experimental data to validate the hypothesis. The RNA polymerase, [ 134 ] as well as the nucleocapsid, [ 135 ] and envelope protein [ 136 ] were proposed as a druggable target, but these studies will require further confirmation by experimental data to verify whether NSPs could be considered viable targets.…”