Screening of inhibitors as potential remedial against Ebolavirus infection: pharmacophore-based approach

Abstract

Abstract Ebola virus disease (EVD) has been recognized as a major threat for humans and primates. Till now, therapeutic solution is a challenging for the treatment of Ebola virus disease. Therefore, new, novel with suitable effective antiviral drug against EVD is essential. In the present study pharmacophore modeling, 3DQSAR, molecular docking, DFT and molecular dynamic simulations were used to identify the new, novel with suitable effective potential inhibitors against Ebola virus through the computational methods. From the pharmacophore PHASE modeling, the best five hypothesis pharmacophore features such as three hydrogen bond acceptor, one positive ion and one aromatic ring are taken to study the 3D-QSAR structural model. The designed with correlation co-efficient is found to be R2\u2009=\u20090.92 and the excellent predictive power with correlation co- efficient is found to be Q2\u2009=\u20090.82. The 3D-QSAR model is used to study the virtual screening against the chemical libraries compounds (NCI, ZINC, Asinex, LifeChemical, ChemBridge, MayBridge, Enamine and specs) to identify the novel scaffolds. The best binding free energy (39.368769\u2009kcal/mol) and the best docking score (12.419\u2009kcal/mol) for NCI database are obtained from molecular docking and MM-GBSA respectively. The good electronic features of ligands are observed from DFT analysis. Finally, molecular dynamics simulations revealed the stability of ligand protein complexes ranging from 1\u2009nm to 1.5\u2009nm. We anticipated that, this ligand protein complex could be supportive to improve the potent inhibitor against the Ebola viral treatment. Communicated by Ramaswamy H. Sarma.