title: An RNA ligand inhibits hepatitis C virus NS3 protease and helicase activities.
abstract: The hepatitis C virus non-structural protein 3 (HCV NS3) possesses both protease and helicase activities that are essential for viral replication. In a previous study, we obtained RNA aptamers that specifically and efficiently inhibited NS3 protease activity (G9 aptamers). In order to add helicase-inhibition capability, we attached (U)14 to the 3'-terminal end of a minimized G9 aptamer, DeltaNEO-III. NEO-III-14U was shown to inhibit the NS3 protease activity more efficiently than the original aptamer and, furthermore, to efficiently inhibit the unwinding reaction by NS3 helicase. In addition, NEO-III-14U has the potential to diminish specific interactions between NS3 and the 3'-UTR of HCV-positive and -negative strands. NEO-III-14U showed effective inhibition against NS3 protease in living cells.
authors.affiliation: Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305-8566, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Fukuda
authors.forename: Takuya
authors.initials: T
authors.lastname: Umehara
authors.forename: Satoru
authors.initials: S
authors.lastname: Sekiya
authors.forename: Kikuchi
authors.initials: K
authors.lastname: Kunio
authors.forename: Tsunemi
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nishikawa
mesh_terms: D001665:Binding Sites; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D010447:Peptide Hydrolases / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding; D012313:RNA / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D020365:RNA Helicases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D008024:Ligands; D010447:Peptide Hydrolases; D012313:RNA; D020365:RNA Helicases; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases