A theoretical model was developed to allosterically inhibit the biological activity of dengue virus (DENV) by targeting the non-structural protein ns2B-nsP3 protease based on the in silico studies. The imidazole, oxazole, triazole, thiadiazole, and thiazolidine based scaffolds were imported from the ZINC database, reported by various research group with different biological activity. They were found biologically active as they contain heterocyclic fragments. Generic evolutionary based molecular docking was performed to screen the highly potent molecule. The docking results show that the molecule having ZINC ID-633972 is best inhibitor. Further, the bioavailability and other physiochemical parameters were also calculated for the top four molecule. The highly potent molecule was further refined by the density functional theory and molecular dynamic (MD) simulation. The MD analysis coroborate the successful docking of the molecule in the binding cavity of nsP2B-nsP3 protease of DENV. The Molecular Mechanics Poisson-Boltzmann Surface Area approach was also applied and result coroborate the docking and MD result.
Keywords: Dengue virus; Density functional theory; Docking; Imidazole; Simulation; Theoretical chemistry; Thiazolidines; ZINC database.