The euHCVdb Suite of In Silico Tools for Investigating the Structural Impact of Mutations in Hepatitis C Virus Proteins

c.      Combet; E.      Bettler; R.      Terreux; N.      Garnier; G.      Deleage

Abstract

Hepatitis C is a viral infection of the liver that results in acute hepatitis and chronic liver disease, including cirrhosis and liver cancer. An estimated 170 million persons are chronically infected worldwide. The Hepatitis C virus is the pathogen agent responsible for hepatitis C. HCV is an enveloped RNA-positive virus of the flaviviridae family. The HCV genome shows remarkable sequence variability. This variability leads to the classification of HCV into 6 genotypes, numerous subtypes and HCV exists in each infected patient as quasi-species. The genotype may be linked to the severity of the disease and to the efficiency of the combination treatment with interferon and ribavirin. To date, no vaccine to prevent or cure HCV exists. Numerous HCV specific inhibitors have been designed and some are currently under clinical trials. However, resistances of HCV against these inhibitors have been identified. We developed the European Hepatitis C Virus Database (euHCVdb, http://euhcvdb.ibcp.fr/), a collection of functionally and structurally (3D-models) annotated HCV sequences integrated with sequence and structure analysis tools. We show below how the euHCVdb database is a useful in silico tool that can help drug design, combating resistance to drug treatment and understand structural biology of the HCV.

Keywords: Hepatitis C Virus, drug design, molecular modelling, database, resistance, virus, sequence analysis, structure analysis