Figure 8. Late Stage Inhibitors.

Inhibitors that showed enhanced potency in the multi-cycle virus replication assay (Inhs 14–16) were tested for their ability to block the production of infectious virus. A. Control inhibitors that block virus entry (EI) and genome replication (BMS-339) inhibited Renilla luciferase expression in both producer (black bars) and target (gray bars) cells while a control late-stage inhibitor (LY411575) only affected Renilla luciferase expression in target cells. Similar to LY411575, Inhs 14–17 exhibited less than 20% inhibition of Renilla luciferase expression in producer cells but >75% inhibition in target cells suggesting a block in the production of infectious virus. B. Genotype coverage was assessed by comparing the potency (EC₅₀) of Inhs 14–17 and LY411575 against HCVcc with genotype 1a, 1b or 2a structural proteins.