The NS5A Replication Complex Inhibitors: Difference Makers?

The development and approval of direct-acting antiviral agents looks set to transform the treatment of chronic hepatitis C infection. Among the agents in development are novel compounds that inhibit the function of the NS5A protein: a pleiotropic protein with a complex and essential role in viral replication. Preclinical studies have demonstrated the potency of these agents across a broad range of viral genotypes, and in early phase trials, they rapidly suppressed viral replication when administered as monotherapy or in combination with pegylated interferon-alpha and ribavirin. The discovery and development of NS5A replication complex inhibitors is summarized in this review.