Computational exploration of antiviral activity of phytochemicals against NS2B/NS3 proteases from dengue virus

Background: Dengue fever has emerged as a serious threat in Pakistan in the last few years with high morbidity rates and substantial mortality. In the present study, NS2B/NS3 protease from four dengue virus (DENV) serotypes have been targeted using 2350 phytochemicals from various medicinal plants. Material and methods: The phytochemicals were subjected to docking against NS2B/NS3 proteases using AutoDock Vina focusing the binding site, and the binding energies were determined to screen the effectively docked phytochemicals. Pharmacological properties were also analyzed for all the phytochemicals using PreADMET web server. Results: Binding affinities ranged from -4.0 to -9.8 kcal/mol and a threshold of -9.0 kcal/mol was applied for screening compounds. A total of 18 phytochemicals are screened for passing all evaluation criteria of a drug in which three were for DENV1-NS2B/NS3, five for DENV2-NS2B/NS3, six for DENV3-NS2B/NS3 and four for DENV4-NS2B/NS3. Erycristagallin and Osajin from Erythrina variegate, PapraineA from Fumaria indica and Aloe-Emodin from Aloe vera are the most potent inhibitors of NS2B/NS3 protease from DENV1, DENV2, DENV3 and DENV4, having binding affinities of -9.6 kcal/mol, -9.6 kcal/mol, -9.6 kcal/mol and -9.2 kcal/mol, respectively. Conclusion: The effective drug-like properties of all 18 phytochemicals demonstrate the inhibition potential against dengue virus replication in human beings.