An Investigation of Fucoidan as a Potential Inhibitor Against DENV/NS3 Proteases Through Molecular Dynamics Simulations and DFT Studies

Abstract Dengue virus (DENV) is a mosquito-borne disease that spreads in the tropics and subtropics mainly by the Aedes aegypti mosquito, infecting more than 100 million people and cause copious deaths every year in globally. As of now, no direct-acting antiviral drugs or vaccine are available to combat DENV. Therefore, identification of novel small molecules from natural origin becomes inevitable for the management of DENV fever. Here, in silicofromPadinagymnospora was analyzed for competitive binding on the active site non-structural protein NS3 proteases were selected that are potential therapeutic target for direct-acting antiviral. The fucoidan compound was docked with active site of NS3 proteases, showing good docking score and strong interaction with the catalytic dyad His51, Asp75 and Ser135 amino acids. Furthermore, Binding Free Energy was done by using prime MM/GBSA to access the binding affinity of fucoidan towards the target protein. Moreover, Molecular Dynamic Simulation was performed to evaluate the structural stability of the docked complexes. In addition, HOMO and LUMO for fucoidan phytocompound was done by DFT calculation, reveals the good chemical stability based on the energy value. The fucoidan phytocompound has satisfied all the relevant pharmacokinetic properties and also highly absorbed by the gastrointestinal tract. From the overall findings of this study, it is concluded that the fucoidan from Padinagymnospora has effectively blocked the catalytic dyad of NS3 proteases which could be considered as a potent inhibitor to control the DENV multiplication infection. Insilico approach plays vital role in the initial screening of lead molecules.