In silico study of possible Marburg virus VP35 inhibitors using structure based virtual screening, ADMET, stability approach via DFT and molecular dynamics simulations

Abstract

This work mainly focused on the valorization of reported metabolites from Maesa perlarius plant to generate only derivatives of optimal molecules, followed by structure-based virtual screening (SBVS), ADMET, DFT and molecular dynamics studies to suggest possible MARV “Marburg virus” VP35 inhibitors. The results indicated the drug candidacy of a single ligand after using several screening steps between score limits, e-pharmacophore screening and fitness constraints, ADMET profile, the CID_144548213 scored −5.414 kcal/mol when glide xp docking compared to a control (Remdesivir) which scored −5.282 kcal/mol. Notwithstanding the relative difference in chemical stability observed compared to the control, due to both the band gap and the extra-precision docking energies, a clear advantage in the pharmacological profile was noted for the top hit molecule, a satisfactory result considering a new study related to such viral phenomenon. The chemical descriptors were determined based on DFT to examine the chemical reactivity. The molecular dynamics confirmed that the top hit molecule CID_144548213 and control molecule held parallel stability profiles, qualifying CID_144548213 as a possible inhibitor of MARV VP35.