title: Antiviral effect of ribonuclease conjugated oligodeoxynucleotides targeting the IRES RNA of the hepatitis C virus.
abstract: Hepatitis C virus (HCV) translation initiation is mediated by a highly structured and conserved RNA, termed the Internal Ribosome Entry Site (IRES), located at the 5'-end of its single stranded RNA genome. It is a key target for the development of new antiviral compounds. Here we made use of the recently developed HCV cell culture system to test the antiviral activity of artificial ribonucleases consisting of imidazole(s) linked to antisense oligodeoxynucleotides targeting the HCV IRES. Results from the cell culture model indicate that the naked antisense oligodeoxynucleotide displayed an efficient antiviral activity. Despite the increased activity observed with the addition of imidazole moieties when tested with the cell-free system, it appears that these improvements were not reproduced in the cellular model.
authors.affiliation: Université de Rennes 1, UPRES JE 2311, INSERM U835, Biochimie Pharmaceutique, 2, Avenue du Prof. Léon Bernard, 35043 Rennes, France.
authors.forename: Carly
authors.initials: C
authors.lastname: Gamble
authors.forename: Maud
authors.initials: M
authors.lastname: Trotard
authors.forename: Jacques
authors.initials: J
authors.lastname: Le Seyec
authors.forename: Valérie
authors.initials: V
authors.lastname: Abreu-Guerniou
authors.forename: Nicolas
authors.initials: N
authors.lastname: Gernigon
authors.forename: Fabienne
authors.initials: F
authors.lastname: Berrée
authors.forename: Bertrand
authors.initials: B
authors.lastname: Carboni
authors.forename: Brice
authors.initials: B
authors.lastname: Felden
authors.forename: Reynald
authors.initials: R
authors.lastname: Gillet
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D001483:Base Sequence; D002460:Cell Line; D002474:Cell-Free System; D016174:Hepacivirus / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000494:pharmacology*; D020319:Oligodeoxyribonucleotides, Antisense / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D012367:RNA, Viral / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism
chemical_list: D020121:5' Untranslated Regions; C542898:5' bis-imidazole AS-ODN; D000998:Antiviral Agents; D007093:Imidazoles; D009838:Oligodeoxyribonucleotides; D020319:Oligodeoxyribonucleotides, Antisense; D012367:RNA, Viral; C029899:imidazole