Due to the lack of a culture system for infectious hepatitis C virus (HCV), the search for new HCV drugs has been greatly hampered.  Cell-based screens for HCV inhibitors in use today are based on the HCV replicon system, which only targets the RNA replication step of the viral lifecycle and does not encompass viral entry, processing, assembly or secretion.  High-throughput screening (HTS) with an infectious HCV system would cover the complete spectrum of potentially druggable targets in all stages of the HCV lifecycle, and thus have more biological relevance than other cell-based assays.[1]  Moreover, targeting several key processes in the viral life cycle may not only increase antiviral efficacy; more importantly, it may also reduce the capacity of the virus to develop resistance to the compound.[2]  Here we describe the development of ML391 , a potent HCV inhibitor developed using the infectious screening platform above and possessing a novel mode of action different from known antivirals for HCV.Hu, Z; Lan, K.H; He, S.; Swaroop, M.; Hu, X.; Southall, N.; Zheng W.; and Liang, T.J. Novel cell-based hepatitis C virus infection assay for quantitative high-throughput screening of anti-hepatitis C virus compounds. Antimicrob. Agents Chemother. 2014 , 58, 995-1004.Liang, T.J.; Ghany, M.G. Current and future therapies for hepatitis C virus infection resistance to direct antiviral agents in patients with hepatitis C virus infection. N. Engl. J. Med.  2013 , 368, 1907-1917.

Discovery of inhibitors of the hepatitis C virus using a cell-based infection assay

248th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.