Hepatitis C virus (HCV), a member of the Flaviviridae family of viruses in the Hepacivirus genus, is encoded by a 9.6-kb positive-strand RNA genome. MK-5172 is a selective inhibitor of HCV NS3/4a protease with broad activity across genotypes and resistant variants. In biochemical assays, MK-5172 demonstrated subnanomolar potency against a panel of major genotypes and variants engineered with common resistant mutations observed in clinical studies. In the replicon assay, MK-5172 demonstrated subnanomolar to low-nanomolar EC50s against genotypes 1a, 1b, and 2a. In chronically HCV-infected chimpanzees, the viral titer was suppressed an additional log with MK-5172 treatment (1 mg/kg; twice daily for 7 days). Liver drug concentrations 12 h after final doses were also ~4-fold higher with MK-5172, at 1.97 μM compared to 0.54 μM with vaniprevir, indicating better drug exposure at the site of HCV replication[3].
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