The Construction Of A Mouse Model For Identifying Inhibitors Targeting HCV IRES And NS3 Serine Protease

Hepatitis C virus (HCV) represents a major health concern, with the number of HCV-infected individuals estimated to be 170 million worldwide. It becomes persistent among 50 to 80% infected persons, and such patients may develop chronic hepatitis and cirrhosis, some may even progress to the stage of hepatocellular carcinoma.Today's therapies based on IFN-α coupling with ribavirin can induce a sustained virological and biochemical response in less than 50% of treated patients, depending on the virus genotypes, the virus load and the patient's age. So the development of a new way for HCV prevention and treatment is very desirable.HCV is a blood-borne enveloped RNA-containing member of the Flavivirus family, approximately 9.6 kb in length. It contains a single large open reading frame (ORF). The HCV ORF encodes a polypeptide of about 3010 amino acid residues. This polypeptide has been suggested to be proteolyticaly processed into 10 viral proteins. Among these proteins, C,E1,E2 and P7 were considered to be structure proteins, and NS2,NS3,NS4A,NS4B,NS5A,NS5B non-structure (NS) proteins. The 5' UTR represents the most conserved region of the genome.lt forms the highly structured internal ribosome entry site (IRES),which directs translation in a cap-independent manner. The N terminus of NS3 protein contains a serine protease domain that forms a tight non-covalent complex with the cofactor NS4A. The C-terminal two-thirds of NS3 protein possess helicase and NTPase activity. These vital functions make IRES and NS3 as two potential drug targets in anti-HCV research.