Efficacy of phytochemicals derived from Artocarpus heterophyllus (Jackfruit) as inhibitors against NS2B/NS3 protease of dengue virus: an in-silico investigation.

Dengue virus is one of the most significant emerging viruses that cause dengue fever, dengue hemorrhagic disease and dengue shock syndrome, threatening one-third of the world’s population. There are currently no vaccinations or antiviral therapies available for this disease. Dengue virus protease (NS2B-NS3pro) is a therapeutic target since it is essential for viral processing and replication. The study aimed to describe an in-silico analysis to uncover efficient Dengue virus inhibitors. In this work, we used computer-assisted virtual screening, ADMET and molecular dynamics-based analysis focus using the NS2B-NS3 protease to find effective Dengue virus inhibitors. Through literature mining, forty-seven phytochemicals from Artocarpus heterophyllus (Jackfruit) were retrieved and screened against the targeted protein. According to their binding free energy in MM-GBSA, Oxidihydroartocarpesin (-36.19 kcal/mole), Cyanomaclurin (-34.09 kcal/mole) and Dihydromorin (-32.44 kcal/mole) were expected to be potent inhibitors of the NS2B-NS3 protease. These ligands showed several noncovalent interactions with the catalytic triad (His51-Asp75-Ser135), required for the target protein inhibition. Notably, the ligand-bound complexes exhibited lower RMSD values (≈ 0.18–0.25 nm) compared to the apo protein (≈ 0.30 nm), indicating enhanced structural stability upon ligand binding. RMSF analysis further demonstrated reduced flexibility around the catalytic residues His51, Asp75, and Ser135 in the presence of the selected phytochemicals, while stable radius of gyration and solvent-accessible surface area profiles confirmed compact and well maintained protein-ligand conformations throughout the simulation period. Additionally, the ligand-bound systems maintained a consistent radius of gyration (~ 1.85–1.90 nm) and sustained an average of 3–6 intermolecular hydrogen bonds throughout the simulation, further supporting the structural integrity and dynamic stability of the complexes relative to the apo form. As a consequence, our computational analysis may be useful in the future development of Dengue Virus inhibitors.