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Oligonucleotides derived from the packaging signal at the 5′ end of the viral PB2 segment specifically inhibit influenza virus in vitro

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Abstract

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.

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Acknowledgments

We thank Prof. Mauro Bendinelli, Department of Experimental Pathology, University of Pisa, Italy, for the critical review of the manuscript. This study was supported in part by grants from the Fondazione “Istituto di Ricerca Virologica Oretta Bartolomei Corsi” and from the Ente “Cassa di Risparmio di Firenze”, Florence, Italy.

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Authors and Affiliations

  1. Virology Unit, Department of Public Health, University of Florence, Viale Morgagni 48, 50134, Florence, Italy

    Simone Giannecchini, Valeria Clausi & Alberta Azzi

  2. Department of Anatomy, Histology and Forensic Medicine, University of Florence, 50134, Florence, Italy

    Daniele Nosi

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  1. Simone Giannecchini
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  2. Valeria Clausi
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  3. Daniele Nosi
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  4. Alberta Azzi
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Correspondence to Simone Giannecchini.

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Giannecchini, S., Clausi, V., Nosi, D. et al. Oligonucleotides derived from the packaging signal at the 5′ end of the viral PB2 segment specifically inhibit influenza virus in vitro. Arch Virol 154, 821–832 (2009). https://doi.org/10.1007/s00705-009-0380-2

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  • DOI: https://doi.org/10.1007/s00705-009-0380-2

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