IDENTIFICATION OF INHIBITORS OF DENGUE VIRUS (DENV1, DENV2 AND DENV3) NS2B/ NS3 SERINE PROTEASE: A MOLICULAR DOCKING AND SIMULATION APPROACH
Abstract
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Dengue is one of the fatal diseases, which are becoming a global health burden from few decades. Dengue fever, dengue hemorrhagic fever and
dengue shock syndrome, caused by dengue virus (DENV), which completes its life cycle in mosquito i.e. Aedes aegyti, and human (DENV), and infect
about various individuals every year. The objective of this study is to find a potent inhibitor of DENV (DENV1, DENV2 and DENV3). In the present
study, NS2b/NS3 serine protease complex in targeted for the screening of the suitable inhibitors for DENV (DENV1, DENV2 and DENV 3). Therefore,
the NS2b/NS3 serine protease complex structures were retrieved from the RCSB Protein Databank. The unliganded protein structures were docked,
and best three selected and analyzed. A molecular dynamic simulation is also performed to investigate the conformational and positional changes
of ligand that provide insights into the binding stability. It was observed that three of screened compounds have the maximum potential against the
protein. The analysis was performed on the basis of scoring and binding ability and one of them indicated minimum energy score with high number
of interactions with active site residues and the simulation study revealed that this selected ligand could efficiently bind to the NS2b/NS3 protease.
These findings conclude that this selected ligand could be a promising inhibitor of all three serotypes of DENV as drug targets.
Keywords: Dengue virus, Aedes aegyti, Flaviviridae, Serine protease, Docking.
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