title: Genotypic analysis of HCV 1a by sequencing of the NS3 proteasic region in simeprevir therapy candidates.
abstract: Each phase of the HCV replication cycle can represent a therapy target. In fact, SIMEPREVIR (SMV) acts as NS3/4A protease inhibitor (PI); its efficacy is, however, reduced in HCV1a patients characterized by NS3Q80K polymorphism. The aim of this work was to design a genotypic analysis of NS3 protease in order to characterize viral quasispecies in HCV 1a patients before starting the SMV therapy. In all, 38 peripheral blood-EDTA samples were collected from patients infected with HCV 1a (RNA > 10,000 cp/ml). The samples were sequenced in a region of 543 nucleotides, codifying for 181 amino acids of the NS3 protease with ABI PRISM 3130xl Genetic Analyzer (Applied Biosystems). Of the 38 samples, two showed the Q80K mutation associated with resistance to SMV. In 16 samples mutations associated with a possible resistance to protease inhibitor, TELAPREVIR, were observed. Only one sample showed the T54S mutation, which is responsible for resistance to BOCEPREVIR, a protease inhibitor too. The data reported in this paper show a 5% prevalence of the Q80K mutation in HCV 1a patients. So far, some differences in the percentage of the Q80K mutations were observed within the European population, when compared with its US counterpart. The prevalence study described herein, albeit observed on a low number of samples, could challenge the recommendations reported in the technical data sheet of SMV.
authors.affiliation: V U.O.C., Azienda Ospedaliera Specialistica dei Colli Monaldi - Cotugno - C.T.O., Napoli, Italy.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Liberti
authors.affiliation: U.O.C. Microbiologia e Virologia, Azienda Ospedaliera Specialistica dei Colli Monaldi - Cotugno - C.T.O., Napoli, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Raddi
authors.affiliation: U.O.C. Microbiologia e Virologia, Azienda Ospedaliera Specialistica dei Colli Monaldi - Cotugno - C.T.O., Napoli, Italy.
authors.forename: Nunzia
authors.initials: N
authors.lastname: Cuomo
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009842:Oligopeptides / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D011480:Protease Inhibitors / Q000627:therapeutic use; D000069616:Simeprevir / Q000627:therapeutic use; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D009842:Oligopeptides; D011480:Protease Inhibitors; D000069616:Simeprevir; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C486464:telaprevir