In silico identification of cyclosporin derivatives as potential inhibitors for RdRp of rotavirus by molecular docking and molecular dynamic studies

Abstract

Rotavirus is one of the most common gastrointestinal viral diseases. Till date, there are only two vaccines available in the markets, which are specifically to be administered to young babies. In this study, VP1 RdRp is selected as potential target to carry out inhibitory activities. Cyclosporin A (Cys A) derivatives were designed via FBDD, pharmacokinetics, molecular docking, molecular dynamics (MD) simulation and molecular mechanics generalized born surface area was applied on these compounds. The results from these investigations were analyzed and it was found that the considered derivatives in this study were nontoxic and docking results revealed that the derivatives made some important bonds inside the active site of the receptors within a catalytic triad (Serine–Histidine–Aspartate). After analyzing the mean values of root mean square density (RMSD), root mean square fluctuation (RMSF), radius of gyration (RoG) and solvent accessible surface area (SASA) at 100 ns MD simulation of the selected compounds, it was found that compound 1 exhibits RMSD of 0.74 ± 0.10 Å, RMSF of 0.85 ± 0.15 Å, RoG of 16.45 ± 0.40 Å, SASA of 66.55 ± 0.35 nm2 and ΔGbind of −32.76 ± 0.02 kcal/mol. Therefore, the study revealed that amongst the designed and reported compounds, compound 1 was more stable within the active region of the RdRp and also this compound possesses lower binding free energy as compared to other selected compounds and Cys A as well. Communicated by Ramaswamy H. Sarma