Drug discovery targeting NS2B-NS3 proteases from dengue and Zika viruses - II

• Main Author: Chan, Kwok Fong
• Other Authors: Mu Yuguang
• Format: Final Year Project
• Language: English
• Published: 2017
• Subjects: DRNTU::Science::Biological sciences
• Online Access: http://hdl.handle.net/10356/72452
• Institution: Nanyang Technological University

The advancement in algorithms and tools for virtual screening has greatly expedited the process of screening libraries. Recent studies have focused on a prospective group of Zika Virus proteases to circumvent the proliferation of the microcephaly- causing virus and to narrow the range of screening targets. Here, structural based virtual screening approach on the Flavivirus NS2B-NS3 protease was adopted in order to identify ligands which could potentially inhibit the protease activity. Multiple Receptor Conformation screening workflow was applied through the sampling of initial structure at different random initial velocities by molecular dynamics to account for the flexibility of the receptor. Conformations of the protein were clustered and the central structure in the cluster were selected as representatives. Molecules from virtual screening libraries such as ChemBridge and Enamine were docked to representative structures using GOLD docking software, and a list ranked in the common top 100 molecules were shortlisted for molecular simulations. Shortlisted ligand from the gathered data have been subjected to protein-ligand complex molecular simulations and the results showed that the molecule remains stable in NS2B-NS3 binding cleft. Further experimental studies can be performed to validate the inhibitors identified.