New antiviral agents for hepatitis C.

Approximately 120-130 million individuals are chronically infected with hepatitis C virus (HCV) worldwide, although it is curable by therapy. Until recently, treatment of chronic hepatitis C was based on the combination of pegylated interferon-α and ribavirin. A number of models have been developed to study the HCV lifecycle and screen for potential HCV inhibitors. They led to the development of antiviral agents that specifically target a viral function (direct acting antivirals), and host-targeted agents that inhibit HCV replication. Direct acting antivirals in clinical development include NS3-4A protease inhibitors (two of which, telaprevir and boceprevir, have recently been approved for treatment of HCV genotype 1 infection in combination with pegylated interferon-α and ribavirin), nucleoside/nucleotide analogue and non-nucleoside inhibitors of HCV RNA-dependent RNA polymerase, and NS5A inhibitors. Host-targeted agents include cyclophilin inhibitors. This article describes the direct acting antivirals and host-targeted agents that have recently been approved or have been tested in HCV-infected patients and discusses their two current paths of clinical development: with or without interferon-α.