title: [Design of deoxyribozymes for inhibition of influenza A virus].
abstract: Influenza A viruses take a significant place in human and animal pathology causing epidemics and epizootics. Therefore, the development of new antiflu drugs has become more and more urgent. Deoxyribozymes can be considered as promising antiviral agents due to their ability to efficiently and highly specifically cleave RNA molecules. In this study, a number ofgenomic sequences of the most relevant influenza A virus subtypes, H5N1, H3N2, and H1N1, were analyzed. Conservative regions were revealed in five the least variable segments of the fragmented viral RNA genome, and potential sites of their cleavage with "10-23" deoxyribozymes were determined. 46 virus-specific 33-mer deoxyribozymes with the general structure of 5'N8AGGCTAGCTACAACGAN9 were designed and synthesized. Screening of the antiviral activity of these agents in conjugation with lipofectin on the Madin-Darby Canine Kidney cells infected with highly pathogenic avian influenza virus A/chicken/Kurgan/05/2005 (H5N1) revealed 17 deoxyribozymes, which suppressed the titer of virus cytopathicity by more than 2.5 IgTCID50/mL (i.e. the virus neutralization index was more than 300), with five of them suppressing the virus titer by a factor of 1000 and more. The most active deoxyribozymes appeared to be specific to segment 5 of the influenza A virus genome, which encoded nucleoprotein (NP).
authors.forename: A A
authors.initials: AA
authors.lastname: Evdokimov
authors.forename: N A
authors.initials: NA
authors.lastname: Mazurkova
authors.forename: E G
authors.initials: EG
authors.lastname: Malygin
authors.forename: V F
authors.initials: VF
authors.lastname: Zarytova
authors.forename: A S
authors.initials: AS
authors.lastname: Levina
authors.forename: M N
authors.initials: MN
authors.lastname: Repkova
authors.forename: S N
authors.initials: SN
authors.lastname: Zagrebelnyĭ
authors.forename: N A
authors.initials: NA
authors.lastname: Netesova
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D021881:DNA, Catalytic / Q000138:chemical synthesis / Q000494:pharmacology*; D004277:DNA, Single-Stranded / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity; D007251:Influenza, Human / Q000188:drug therapy / Q000235:genetics; D061985:Madin Darby Canine Kidney Cells / Q000187:drug effects; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D021881:DNA, Catalytic; D004277:DNA, Single-Stranded; D012367:RNA, Viral; C402582:RNA-cleaving DNA 10-23