DEVELOPMENT OF INHIBITORS AGAINST HCV INFECTION

DESCRIPTION (Provided by applicant): Hepatitis C viral infection is the most common chronic bloodborne infection in the United States. There are about 36,000 new infections every year, and 25-30 percent of those infections are symptomatic. It is estimated that 3.9 million (1.8 percent) Americans have been infected. Chronic liver disease, which is caused by HCV infection, is the tenth leading cause of death among adults in the United States, accounting for approximately 1 percent of all deaths. To date, there is no efficient culture system available to evaluate the activity of compounds against HCV in vitro. To overcome this difficulty, surrogate animal viruses are being used, including bovine viral diarrhea virus, yellow fever virus, dengue virus, and banzi virus. We have identified a compound (ZX-2401) that shows a significant antiviral activity against these surrogate viruses. The overall scope of this application is to investigate the feasibility of this compound and its derivatives as potential inhibitors of HCV. The specific aims for these novel compounds include synthesizing ZX-2401 or derivatives as needed for the proposed studies, performing in vitro antiviral studies in HCV replicon system and cytotoxicity testing, performing studies in combination with IFN-alpha, and performing mechanism of action studies.