Drug discovery targeting NS2B-NS3 proteases from dengue and Zika viruses
The advancements in algorithms and tools for virtual screening have greatly expedited the process of virtual screening. Recent studies have focused on a prospective group of Zika Virus (ZIKV) proteases to circumvent the proliferation of the microcephaly-causing virus. In this research, a structure based virtual screening approach on the ZIKV 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 crystal structure at different random initial velocities by molecular dynamics simulation to account for receptor flexibility. Conformations of the protein were clustered by binding pocket conformations. Molecules from virtual screening libraries such as ChemBridge and Enamine were docked to clustering representative structures using GOLD docking software, and a list of the most common top ranked 100 molecules were shortlisted for molecular simulations. A selected ligand subjected to protein-ligand complex molecular dynamics simulations revealed that the molecule remained stable in NS2B-NS3 binding cleft. Further experimental studies can be performed to validate the inhibitors identified.
Author: Chan KF et al <<< Published on: 30 August 2018