Hepatitis C (HCV)
An estimated 3% of the world's population is infected with Hepatitis C (HCV), a major cause of hepatitis and chronic liver disease, including hepatic steatosis, cirrhosis and hepatocellular carcinoma. More than two-thirds of HCV-infected patients develop a chronic infection, and 10-20% of those patients develop cirrhosis, with 1-5% developing liver cancer over a period of 20 to 30 years. HCV is the major cause of liver transplantation in the USA.
Understanding HCV
HCV was identified in 1989 as a positive-stranded RNA virus distinct from Hepatitis A and Hepatitis B viruses. HCV is transmitted through direct contact with human blood. The major causes of HCV infection are intravenous drug use and unscreened blood transfusions.
Treatment
There is no vaccine against HCV. The current standard of care for patients infected with HCV is treatment with a combination of pegylated interferon and ribavirin. However this treatment is poorly tolerated because of its severe side effects. Furthermore it is effective in less than 50% of those infected with HCV genotype 1, the cause of close to 70% of the chronic HCV infections in North America, Europe and Asia.
Antiviral Targets
Scientists at Boehringer Ingelheim (Canada) Ltd./Ltée. lead the way in the discovery of inhibitors of the HCV NS3 protease and discovered BILN-2061, which was the first specific inhibitor of HCV replication to demonstrate antiviral activity in patients with chronic HCV infection. Our scientists are actively exploring a number of HCV targets, including but not limited to, HCV protease and HCV RNA polymerase, in their efforts to identify specific antiviral therapies for the treatment of this disease.
Suggested Reading
Beaulieu PL.
Non-nucleoside inhibitors of the HCV NS5B polymerase: progress in the discovery and development of novel agents for the treatment of HCV infections. Curr Opin Investig Drugs. 2007 Aug;8 (8):614-34. Review. PMID: 17668364 [PubMed - indexed for MEDLINE]
Beaulieu PL, Gillard J, Bykowski D, Brochu C, Dansereau N, Duceppe JS, Haché B, Jakalian A, Lagacé L, LaPlante S, McKercher G, Moreau E, Perreault S, Stammers T, Thauvette L, Warrington J, Kukolj G.
Improved replicon cellular activity of non-nucleoside allosteric inhibitors of HCV NS5B polymerase: from benzimidazole to indole scaffolds. Bioorg Med Chem Lett. 2006 Oct 1;16(19):4987-93. PMID: 16908138 [PubMed - indexed for MEDLINE]
Beaulieu PL.
Finger loop inhibitors of the HCV NS5B polymerase: discovery and prospects for new HCV therapy. Curr Opin Drug Discov Devel. 2006 Sep;9(5):618-26. Review. PMID: 17002222 [PubMed - indexed for MEDLINE]
Beaulieu PL.
The discovery of finger loop inhibitors of the hepatitis C virus NS5B polymerase: status and prospects for novel HCV therapeutics. IDrugs. 2006 Jan;9(1):39-43. Review. PMID: 16374732 [PubMed - indexed for MEDLINE]
