Poster abstracts

Poster number 113 submitted by M James Ross

Characterization and reactivity of catalytic metallodrugs targeting HCV IRES RNA

M. James Ross (Chemistry and Biochemistry, The Ohio State University), Seth Bradford (Chemistry and Biochemistry, The Ohio State University), Insiya Fidai (Chemistry and Biochemistry, The Ohio State University)

Abstract:
HCV is responsible for 60% of cases of chronic hepatitis and 50% of cases of cirrhosis, end-stage liver disease, and liver cancer. Four million Americans show evidence of HCV infection and the virus causes an estimated 12,000 deaths per year. No effective vaccine is available and the current treatment involving a combination of pegylated recombinant interferon-alpha-2b (rIFNa-2b) and ribavirin has toxicity issues and is nonspecific for HCV. The only therapies that directly target HCV are the recently FDA approved NS3 protease inhibitors telaprevir and boceprevir which are limited to genotype 1 and are susceptible to mutation. Therefore, there is a demand for novel approaches to treatment of HCV infection. The HCV internal ribosomal entry site (IRES) is a highly conserved 5'-untranslated region of HCV mRNA which is folded into complex secondary and tertiary conformations. It is important for initiation of viral translation and it has been shown to be important for the life cycle of the virus with domain II being essential for IRES activity. Catalytic metallodrugs offer a novel approach to inactivation of the IRES through irreversible chemistry. In addition, metallodrugs having the capacity to react with multiple RNA targets and have higher levels of specificity as a result of a double filter selection mechanism where nonspecific binding to other biomolecules does not lead to productive chemistry.

Keywords: HCV, metallodrugs