title: Inhibition of norovirus replication by morpholino oligomers targeting the 5'-end of the genome.
abstract: Noroviruses are an important cause of non-bacterial epidemic gastroenteritis, but no specific antiviral therapies are available. We investigated the inhibitory effect of phosphorodiamidiate morpholino oligomers (PMOs) targeted against norovirus sequences. A panel of peptide-conjugated PMOs (PPMOs) specific for the murine norovirus (MNV) genome was developed, and two PPMO compounds directed against the first AUG of the ORF1 coding sequence near the 5'-end of the genome proved effective in inhibiting MNV replication in cells. A consensus PPMO (designated Noro 1.1), designed to target the corresponding region of several diverse human norovirus genotypes, decreased the efficiency of protein translation in a cell-free luciferase reporter assay and inhibited Norwalk virus protein expression in replicon-bearing cells. Our data suggest that PPMOs directed against the relatively conserved 5'-end of the norovirus genome may show broad antiviral activity against this genetically diverse group of viruses.
authors.affiliation: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, DHHS, 50 South Drive, Bldg. 50, Room 6316, Bethesda, MD 20892, USA. bokk@niaid.nih.gov
authors.forename: Karin
authors.initials: K
authors.lastname: Bok
authors.forename: Victoria J
authors.initials: VJ
authors.lastname: Cavanaugh
authors.forename: David O
authors.initials: DO
authors.lastname: Matson
authors.forename: Lorenzo
authors.initials: L
authors.lastname: González-Molleda
authors.forename: Kyeong-Ok
authors.initials: KO
authors.lastname: Chang
authors.forename: Carmelann
authors.initials: C
authors.lastname: Zintz
authors.forename: Alvin W
authors.initials: AW
authors.lastname: Smith
authors.forename: Patrick
authors.initials: P
authors.lastname: Iversen
authors.forename: Kim Y
authors.initials: KY
authors.lastname: Green
authors.forename: Ann E
authors.initials: AE
authors.lastname: Campbell
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D006801:Humans; D051379:Mice; D009025:Morpholines / Q000494:pharmacology*; D029322:Norovirus / Q000187:drug effects*; D014176:Protein Biosynthesis / Q000187:drug effects; D012367:RNA, Viral / Q000378:metabolism*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D009025:Morpholines; D012367:RNA, Viral
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