Hepatitis C Virus: From Molecular Virology to Antiviral Therapy

Pawlotsky JM, Jean-Michel Pawlotsky

Resolution of the three-dimensional structures of several Hepatitis C virus (HCV) proteins, together with the development of replicative cell culture systems, has led to the identification of a number of potential targets for direct-acting antiviral agents (DAA). Numerous families of drugs that potently inhibit the HCV life cycle in vitro have been identified, and some of these molecules have reached early to late clinical development. Two NS3-4A protease inhibitors, telaprevir and boceprevir, were approved in Europe and the United States in 2011 in combination with pegylated interferon (IFN)-α and ribavirin for the treatment of chronic hepatitis C related to HCV genotype 1. A number of other DAAs are at the clinical developmental stage in combination with pegylated IFN-α and ribavirin or with other DAAs in IFN-free regimens, with or without ribavirin. They include second-wave, first-generation, and second-generation NS3-4A protease inhibitors, nucleoside/nucleotide analogue inhibitors, and non-nucleoside inhibitors of HCV RNA-dependent RNA polymerase, inhibitors of nonstructural protein 5A and host-targeted agents, such as cyclophilin A inhibitors and microRNA-122 antagonists. The proof of concept that IFN-free regimens can lead to HCV eradication has recently been brought. This chapter provides an overview of the current treatment of HCV infection and discusses the future of HCV therapy with new anti-HCV drugs.