title: The science of direct-acting antiviral and host-targeted agent therapy.
abstract: Direct-acting antiviral drugs targeting two major steps of the HCV life cycle, polyprotein processing and replication, and cyclophilin inhibitors, that target a host cell protein required to interact with the replication complex, have reached clinical development. In order to achieve a sustained virological response, that is, a cure of the HCV infection, it is necessary to shut down virus production, to maintain viral inhibition throughout treatment and to induce a significant, slower second-phase decline in HCV RNA levels that leads to definitive clearance of infected cells. Recent findings suggest that the interferon era is coming to an end in hepatitis C therapy and HCV infection can be cured by all-oral interferon-free treatment regimens within 12 to 24 weeks. Further results are awaited that will allow the establishment of an ideal first-line all-oral, interferon-free treatment regimen for patients with chronic HCV infection.
authors.affiliation: National Reference Center for Viral Hepatitis B, C and D, Department of Virology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France. jean-michel.pawlotsky@hmn.aphp.fr
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Pawlotsky
mesh_terms: D000284:Administration, Oral; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D021984:Cyclophilin A / Q000037:antagonists & inhibitors; D004359:Drug Therapy, Combination; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors; D011480:Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D012367:RNA, Viral / Q000187:drug effects*; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors; D019065:Virus Assembly / Q000187:drug effects; D053585:Virus Attachment / Q000187:drug effects; D053586:Virus Internalization / Q000187:drug effects; D057074:Virus Release / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D011480:Protease Inhibitors; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; D012324:RNA-Dependent RNA Polymerase; D021984:Cyclophilin A