PF-429242, an active site-directed small-molecule inhibitor of SKI-1/S1P [64, 84] , was synthesized by Dr. Peter Chua at the Center for Drug Research and Development (CDRD) at the University of British Columbia (Vancouver, BC, Canada) according to previously described protocols [65] . To investigate the antiviral activity of the small molecule, Huh-7.5.1 cells were treated with PF-429242 for 24 hours. After 24 hours of treatment, the media was removed and then cells were infected with HCV (moi 0.1) for 48 or 72 hours. Alternatively, cells were first infected with HCV for 24 hours; then, the media was removed and replaced with media containing various concentrations of PF-429242 for a further 48 hours. Intracellular HCV infection levels were determined using Cellomics HCS ArrayScan. Infectious extracellular titers were determined in media of 72-hour HCVinfected cells.