title: The NS5A replication complex inhibitors: difference makers?
abstract: 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-α and ribavirin. The discovery and development of NS5A replication complex inhibitors is summarized in this review.
authors.affiliation: Division of Gastroenterology, University of California at San Diego, San Diego, CA 92103-8413, USA. rgish@ucsd.edu
authors.forename: Robert G
authors.initials: RG
authors.lastname: Gish
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Meanwell
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002219:Carbamates; D002986:Clinical Trials as Topic; D055808:Drug Discovery; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D011759:Pyrrolidines; D014633:Valine / Q000031:analogs & derivatives; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D011759:Pyrrolidines; D014633:Valine; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C549273:daclatasvir