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Antiviral Activity of Nanocomplexes of Antisense Oligonucleotides Targeting VP72 Protein in Vero Cells Infected by African Swine Fever Virus

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Abstract

Antiviral activity of antisense oligodeoxyribonucleotides with phosphorothioate or mesyl phosphoramidate internucleotidic groups targeting the main capsid protein VP72 mRNA of the African swine fever virus (ASFV), either in a free form with Lipofectamine 3000 transfection or in the form of ionic complexes with amino-modified mesoporous silicon dioxide nanoparticles, has been evaluated in Vero cells infected with ASFV. Relatively high cytotoxicity of oligonucleotide nanocomplexes for Vero cells at concentrations above 500 nM was detected. Two sequences of antisense oligonucleotides were identified, which reduced the virus titer by an order of magnitude at 500 nM. The antiviral effect of nanocomplexes exceeded that of free oligonucleotides in the presence of Lipofectamine 3000, which indicates a more efficient delivery of nanocomplexes to the cells. Antisense oligonucleotides able to reduce the replication of ASFV were hitherto unknown from the literature. The obtained data can be used as a starting point for further research on the development of oligonucleotide-based antiviral drugs against the African swine fever virus.

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ACKNOWLEDGMENTS

Authors thank Dr. Е.А. Zelentsova (The Centre for Collective Use for Mass Spectroscopy Studies of the International Tomographic Centre, Siberian Branch of the Russian Academy of Sciences) for MALDI-TOF spectra of oligonucleotides.

Funding

The work was funded by Russian Foundation for Basic Research (grant no. 18-515-05007), and the Ministry of High Education and Science of the Russian Federation (project of Novosibirsk State University FSUS-2020-0035).

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Authors and Affiliations

  1. Institute of Molecular Biology of the National Academy of Sciences of the Republic of Armenia, 0014, Yerevan, Armenia

    A. V. Hakobyan, E. A. Arabyan, A. R. Kotsinyan & O. S. Zakaryan

  2. Novosibirsk State University, 630090, Novosibirsk, Russia

    E. A. Burakova, A. A. Fokina & D. A. Stetsenko

  3. Institute of Cytology and Genetics SB RAS, 630090, Novosibirsk, Russia

    E. A. Burakova, A. A. Fokina & D. A. Stetsenko

  4. Institute of Chemical Biology and Fundamental Medicine SB RAS, 630090, Novosibirsk, Russia

    S. V. Vasilyeva

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  1. A. V. Hakobyan
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  2. E. A. Burakova
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  3. E. A. Arabyan
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  4. A. A. Fokina
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  5. A. R. Kotsinyan
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  6. S. V. Vasilyeva
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  7. O. S. Zakaryan
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  8. D. A. Stetsenko
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Contributions

А.V. Akobyan and Е.А. Burakova contributed equally to the work.

Corresponding author

Correspondence to D. A. Stetsenko.

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This work contains no description of studies carried out by any of the authors that involve humans or animals.

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Additional information

Abbreviations: APTES, 3-aminopropyltriethoxysilane; СТАВ, cetyltrimethylammonium bromide; DMTr, 4,4'-dimethoxytrityl; MALDI-TOF, matrix assisted laser desorption ionization time of flight mass spectrometry; TCID50, median tissue culture infection dose; TEAA, triethylammonium acetate; АSF, African swine fever. All oligonucleotide sequences are 5'–3'; prefix d in oligodeoxyribonucleotides is omitted.

Corresponding author: phopne: +7 (383) 363-49-63.

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Hakobyan, A.V., Burakova, E.A., Arabyan, E.A. et al. Antiviral Activity of Nanocomplexes of Antisense Oligonucleotides Targeting VP72 Protein in Vero Cells Infected by African Swine Fever Virus. Russ J Bioorg Chem 47, 411–419 (2021). https://doi.org/10.1134/S1068162021020035

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