Oligonucleotides derived from the packaging signal at the 5' end of the viral PB2 segment specifically inhibit influenza virus in vitro.
The development of new antiviral molecules to fight the possible emergence of influenza viruses with pandemic potential is needed. In this study, phosphorothioate oligonucleotides (S-ONs) derived from the packaging signals in the 3' and 5' ends of the viral PB2 RNA were associated with liposomes and tested against influenza virus in vitro. A 15-mer S-ON derived from the 5' end of the viral PB2 RNA, complementary to the 3' end of its coding region (nucleotides 2279-2293) and designated 5-15b, proved markedly inhibitory. The antiviral activity of 5-15b was dose- and time-dependent but was independent of the cell substrate and multiplicity of infection used. Importantly, inhibition of influenza A and B viruses required S-ONs reproducing the respective packaging signals. Furthermore, 5-15b and its antisense derivative S-ON activity did not affect intracellular accumulation of viral RNA. Confocal microscopy showed that 5-15b is clearly nucleophilic. These findings indicate that the packaging signal at the 5' end of the PB2 RNA is an interesting target for the design of new anti-influenza-virus compounds.
Virology Unit, Department of Public Health, University of Florence, Viale Morgagni 48, 50134 Florence, Italy. simone.giannecchini@unifi.it
Simone
S
Giannecchini
Valeria
V
Clausi
Daniele
D
Nosi
Alberta
A
Azzi
D000818:Animals; D001483:Base Sequence; D002522:Chlorocebus aethiops; D004285:Dogs; D009980:Influenza A virus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D009981:Influenza B virus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D008081:Liposomes / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009976:Orthomyxoviridae Infections / Q000188:drug therapy; D054735:Phosphorothioate Oligonucleotides / Q000494:pharmacology*; D012367:RNA, Viral / Q000235:genetics; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics*; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics*; D014779:Virus Replication / Q000187:drug effects
D008081:Liposomes; C057027:PB2 protein, Influenzavirus A; D054735:Phosphorothioate Oligonucleotides; D012367:RNA, Viral; D014764:Viral Proteins; D012324:RNA-Dependent RNA Polymerase