title: Inhibition of influenza virus replication by phosphorothioate oligodeoxynucleotides.
abstract: Oligodeoxynucleotides (ODNs) were synthesized and tested for their antiviral activity against influenza viruses. ODNs corresponded to the polymerase PB1 gene of either influenza A/WSN/33 virus or influenza C/JJ/50 virus. All compounds were 20 nucleotides long, including control ODNs containing mismatches. The phosphodiester ODNs (O-ODNs) failed to inhibit replication of influenza A and influenza C viruses at concentrations up to 80 microM, possibly due to intracellular nuclease digestion of the unmodified oligomers. By contrast, the phosphorothioate derivatives (S-ODNs) were found to inhibit replication of both influenza A and influenza C virus. The antiviral effect of S-ODNs against influenza A virus was found at concentrations as low as 1.25 microM and was present with mismatched oligomers. In the case of influenza C virus, the S-ODN complementary to the 3' end of the viral RNA of the PB1 gene revealed a sequence-specific antiviral activity at a concentration of 20 microM. (At the same concentration, S-ODNs with one or three mismatches showed little or no antiviral activity.) Reduction in plaque number reached six logarithms when this sequence-specific S-ODN was used at a concentration of 80 microM.
authors.affiliation: Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029.
authors.forename: J M
authors.initials: JM
authors.lastname: Leiter
authors.forename: S
authors.initials: S
authors.lastname: Agrawal
authors.forename: P
authors.initials: P
authors.lastname: Palese
authors.forename: P C
authors.initials: PC
authors.lastname: Zamecnik
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis; D001483:Base Sequence; D002460:Cell Line; D009980:Influenza A virus / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D007700:Kinetics; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis / Q000494:pharmacology*; D012367:RNA, Viral / Q000235:genetics; D013329:Structure-Activity Relationship; D013873:Thionucleotides / Q000138:chemical synthesis / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D009838:Oligodeoxyribonucleotides; D012367:RNA, Viral; D013873:Thionucleotides