Chemoinformatic design and profiling of some derivatives of 1, 2, 4-oxadiazole as potential dengue virus NS-5 inhibitors

Abstract Background Dengue virus (DENV) infection is spreading rapidly, especially in the subtropical and tropical regions, placing a huge percentage of global population at risk causing repeated outbreaks. DENV protease inhibition has been suggested as viable therapeutic strategy. Using computer-aided design approach structure-based drug approach, ten 1, 2, 4-oxadiazole derivatives were designed based on lead template (34) from our prior study. The involved substitution phenyl pharmacophore with methylamine, hydroxyl, methoxy groups. To compare anti-DENV efficacy optimized compounds to other referenced inhibitors targeting NS-5 (PDB ID: 5K5M), they docked protease. In silico, ADME characteristics drug-likeness also assessed for compounds. Results molecular docking scores varied ? 19.091 29.61 kcal/mol, excellent hydrogen bond energies range 3.402 9.0128 compared score 19.10 energy 3.10 both which are lower than those proposed Ferentinide, S -adenosyl-l-homocysteine, Ribavirin found have binding 15.8137, 16.5362, 12.446 respectively, 4.2659, 10.4372, 7.2995 kcal/mol. developed all followed Lipinski's criteria, meaning highly bioavailable, had no potential carcinogenic or mutagenic properties, posed concern cardiovascular toxicity ADMET profile. Conclusion oxadiazole derivative interacted better (NS-5) inhibitor well conventional inhibitors. Compounds 34a 34b best ligand-protease interaction gave lowest free 26.54 29.612 respectively. Hence, could be candidates inhibit RdRp This study revealed action compounds, indicating that synthesis vivo studies into their mechanism warranted.