title: Daclatasvir: the first of a new class of drugs targeted against hepatitis C virus NS5A.
abstract: Hepatitis C virus (HCV) infection affects about 160 million people worldwide. It is treated with pegylatedinterferon (peg-IFN) and ribavirin, and in the case of patients affected by genotype 1, also with a protease inhibitor (telaprevir or boceprevir). Despite a good success rate, IFN-based combinations are contraindicated in several patients (e.g. decompensated cirrhosis, patients with psychiatric disorders, severe heart diseases or autoimmune disorders) and are associated with frequent adverse events that ultimately reduce their use. Numerous oral drugs are in an advanced phase of clinical development, and in some cases, in IFN-free combinations. This review focuses on preclinical and clinical data regarding daclatasvir (BMS-790052), which is a highly selective HCV NS5A replication complex inhibitor effective against HCV genotypes 1, 2, 3 and 4. In vitro data show that daclatasvir exerts a very potent antiviral effect against several HCV genotypes. Its pharmacokinetics is optimal and allows once-a-day oral administration. Its adverse event profile is good. Clinical data regarding its efficacy in combination with peg-IFN, ribavirin or other direct antiviral agents are impressive (rates of sustained virological response range between 60% and 100% in treatment-naïve patients). The only drawback of this drug appears to be a relatively low genetic barrier to resistance. In conclusion, daclatasvir, especially in combinations with other antiviral agents, is a very promising drug for the treatment of chronic hepatitis C.
authors.forename: I
authors.initials: I
authors.lastname: Gentile
authors.forename: F
authors.initials: F
authors.lastname: Borgia
authors.forename: N
authors.initials: N
authors.lastname: Coppola
authors.forename: A R
authors.initials: AR
authors.lastname: Buonomo
authors.forename: G
authors.initials: G
authors.lastname: Castaldo
authors.affiliation: Department of Clinical Medicine and Surgery (Ed. 18) - University of Naples "Federico II", via S. Pansini, 5 I-80131 Naples, Italy. ivan.gentile@unina.it.
authors.forename: G
authors.initials: G
authors.lastname: Borgia
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000627:therapeutic use*; D002219:Carbamates; D002986:Clinical Trials as Topic; D004338:Drug Combinations; D016174:Hepacivirus / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000627:therapeutic use*; D011759:Pyrrolidines; D014633:Valine / Q000031:analogs & derivatives; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D004338:Drug Combinations; D007093:Imidazoles; D011759:Pyrrolidines; D014633:Valine; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C549273:daclatasvir