Multiple virtual screening approaches for finding new hepatitis C virus RNA-dependent RNA polymerase inhibitors: structure-based screens and molecular dynamics for the pursue of new poly pharmacological inhibitors.

ABSTRACT: The RNA polymerase NS5B of Hepatitis C virus (HCV) is a well-characterised drug target with an active site and four allosteric binding sites. This work presents a workflow for virtual screening and its application to Drug Bank screening targeting the Hepatitis C Virus (HCV) RNA polymerase non-nucleoside binding sites. Potential polypharmacological drugs are sought with predicted active inhibition on viral replication, and with proven positive pharmaco-clinical profiles. The approach adopted was receptor-based. Docking screens, guided with contact pharmacophores and neural-network activity prediction models on all allosteric binding sites and MD simulations, constituted our analysis workflow for identification of potential hits. Steps included: 1) using a two-phase docking screen with Surfl

SUBMITTER: Elhefnawi M 

PROVIDER: S-EPMC3521232 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature