In-silico Drug Design and In-Silico Screening (Track)




Computer-Aided Drug Design and Drug Discovery Efforts for Hepatitis C Virus: Novel polymerase inhibitors and optimal small interfering RNAs targeting the HCV genome

Mahmoud ElHefnawi
National Research Centre, 12311 Cairo, Egypt

Abstract:

Hepatitis C Virus is a major health problem worldwide and in Egypt. Rational drug design has become an attractive discipline through which many novel drugs have emerged. In this talk, I will highlight some of the recent publications and current efforts in developing novel Hepatitis C inhibitors / gene therapy using the most advanced chemoinformatics techniques. Novel lead candidates based on lead optimization of the RG7127 nucleoside analog and the the Filibuvir (PF-00868554), targeting the HCV polymerase active site have been found by using a ligand-based using Pharmacophor-basedd virtual screening was then performed on the NCI, and Maybridge databases coupled with a structure-based drug design approaches. Also, new potential polymerase inhibitors have been found through virtual screening and docking the Drug Bank and zinc databases using a the Sybil consensus scoring for screening and the extreme precision function for docking. The polymerase binding sites have been studied using structural bioinformatics to determine the most conserved site across genotypes. Moreover, potential optimal siRNAs targeting IRES subdomains critical for translation of the virus have been found which have less than 2 mismatches to all known subtypes and were found through a novel rational methodology that takes into account all factors for efficient siRNA design like target accessibility, scoring, and off-targets. This methodology was implemented in a program that is free for users that takes care of all steps needed for this rational drug design task.