Antiviral effect of ribonuclease conjugated oligodeoxynucleotides targeting the IRES RNA of the hepatitis C virus.
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.
Gamble
Carly
C
Université de Rennes 1, UPRES JE 2311, INSERM U835, Biochimie Pharmaceutique, 2, Avenue du Prof. Léon Bernard, 35043 Rennes, France.
Trotard
Maud
M
Le Seyec
Jacques
J
Abreu-Guerniou
Valérie
V
Gernigon
Nicolas
N
Berrée
Fabienne
F
Carboni
Bertrand
B
Felden
Brice
B
Gillet
Reynald
R
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
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