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Recent advances in prevention and treatment of hepatitis C virus infections
1Infectious Diseases Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.
Abstract:
Hepatitis C virus (HCV) is the leading cause of chronic hepatitis in humans. As members of the flavivirus family, HCVs are a group of small single-stranded, positive-sense RNA viruses. Upon translation of the genome, a polyprotein precursor is synthesized and further processed by both cellular and viral proteases to generate functional viral proteins. Treatment options are currently limited to the administration of alpha-interferon alone or in combination with ribavirin. Unfortunately, these approaches are characterized by relatively poor efficacy and an unfavorable side-effect profile. Therefore, intensive effort is directed at the discovery of novel molecules to treat this disease. These new approaches include the development of prophylactic and therapeutic vaccines, the identification of interferons with improved pharmacokinetic characteristics, and the discovery of novel drugs designed to inhibit the function of three major viral proteins: protease, helicase and polymerase. Finally, the HCV RNA genome itself, particularly the IRES element, is being actively exploited as an antiviral target using antisense molecules and catalytic ribozymes. This review summarizes the most recent findings in each of these areas. Although not intended to be comprehensive, it should serve as a first resource for those individuals who desire updated information in this rapidly changing field.