Antiviral Activity of a New Class of Chemically Modified Antisense Oligonucleotides against Influenza А Virus

  • 3 Accesses


The paper reports the synthesis of a series of antisense oligonucleotides (aONs) directed against different segments of the influenza A virus genome (H1N1) and screening of their antiviral activity in the influenza A virus (H1N1)/MDCK cells and influenza A virus (H1N1)/A549 cells systems. The results of screening have shown that PB1-2AUG-R aON targeted towards the AUG codon region of the segment 2 of virus genome possessed the highest antiviral activity. The synthesized morpholino analog (PMO) and the new phosphoryl guanidine oligodeoxyribonucleotide (PGO) with the sequence of oligonucleotide PB1-2AUG-R provided a comparable biological effects: the influenza virus titer in MDCK cell culture was reduced by 15 times compared to the control when PGO was used in the concentration of 10 µM and by 40 times when PMO was used in the concentration of 20 µM. For the delivery of electrically neutral analogs of oligonucleotides (PGO and PMO), the perforation method proposed for PMO was used.

This is a preview of subscription content, log in to check access.

Access options

Buy single article

Instant unlimited access to the full article PDF.

US$ 39.95

Price includes VAT for USA

Fig. 1.
Fig. 2.


  1. 1

    Drake, J.W. and Holland, J.J., Proc. Natl. Acad. Sci. U. S. A., 1999, vol. 96, pp. 13 910–13 913.

  2. 2

    Domingo, E., Virology, 2000, vol. 270, pp. 251–253.

  3. 3

    Ferguson, N.M. and Anderson, R.M., Nat. Med., 2002, vol. 8, pp. 562–563.

  4. 4

    Palese, P., Basler, C.F., and Garcia-Sastre, A., Nat. Med., 2002, vol. 8, pp. 927–928.

  5. 5

    Wareing, M.D. and Tannock, G.A., Curr. Opin. Pulm. Med., 2002, vol. 8, pp. 209–213.

  6. 6

    Luscher-Mattli, M., Arch. Virol., 2000, vol. 145, pp. 2233–2248.

  7. 7

    Kole, R., Krainer, A., and Altman, S., Nat. Rev. Drug Discov., 2012, vol. 11, pp. 125–140.

  8. 8

    Crooke, S.T., Methods Enzymol., 2000, vol. 313, pp. 3–45.

  9. 9

    Agrawal, S. and Kandimalla, E.R., Curr. Cancer. Drug Targets, 2001, vol. 1, pp. 197–209.

  10. 10

    Zamechnik, P. and Stephenson, M., Proc. Natl. Acad. Sci. U. S. A., 1978, vol. 75, pp. 280–284.

  11. 11

    Stephenson, M. and Zamechnik, P., Proc. Natl. Acad. Sci. U. S. A., 1978, vol. 75, pp. 285–288.

  12. 12

    Hatta, T., Nakagawa, Y., Takai, K., Nakada, S., Yokota, T., and Takaku, H., Biochem. Biophys. Res Commun., 1996, vol. 223, pp. 341–346.

  13. 13

    Hatta, T., Takai, K., Nakada, S., Yokota, T., and Takaku, H., Biochem. Biophys. Res. Commun., 1997, vol. 232, pp. 545–549.

  14. 14

    Abe, T., Hatta, T., Takai, K., Nakashima, H., Yokota, T., and Takaku, H., Nucleosides Nucleotides, 1998, vol. 17, pp. 471–478.

  15. 15

    Duan, M., Zhou, Z., Lin, R.X., Yang, J., Xia, X.Z., and Wang, S.Q., Antivir. Ther., 2008, vol. 13, no. 1, pp. 109–114.

  16. 16

    Ge, Q, Pastey, M., Kobasa, D., Puthavathana, P., Lupfer, C., Bestwick, R.K., Iversen, P.L., Chen, J., and Stein, D.A., Antimicrob. Agents Chemother., 2006, vol. 50, no. 11, pp. 3724–3733.

  17. 17

    Leiter, J.M., Agrawal, S., Palese, P., and Zamecnik, P.C., Proc. Natl. Acad. Sci. U. S. A., 1, vol. 87, no. 9, pp. 3430–3434.

  18. 18

    Abe, T., Mizuta, T., Hatta, T., Miyano-Kurosaki, N., Fujiwara, M., Takai, K., Shigeta, S., Yokota, T., and Takaku, H., Eur. J. Pharm. Sci., 2001, vol. 13, no. 1, pp. 61–69.

  19. 19

    Neumann, G. and Kawaoka, Y., Nat. Rev. Microbiol., 2015, vol. 13, no. 1, pp. 28–41.

  20. 20

    ElHefnawi, M., Alaidi, O., Mohamed, N., Kamar, M., El-Azab, I., Zada, S., and Siam, R., Virol. J., 2011, vol. 8, p. 44.

  21. 21

    Priore, S.F., Kierzek, E., Kierzek, R., Baman, J.R., Moss, W.N., Dela-Moss, L.I., and Turner, D.H., PLoS One, 2013, vol. 8, no. 9. e70615.

  22. 22

    Dirin, M. and Winkler, J., Expert Opin. Biol. Ther., 2013, vol. 13, no. 6, pp. 875–888.

  23. 23

    Peng, H., Wu, Y., and Zhang, Y., PLoS One, 2012, vol. 7, no. 8. e43748.

  24. 24

    Kos, R., Tucker, R.P., Hall, R., Duong, T.D., and Erickson, C.A., Dev. Dyn., 2003, vol. 226, no. 3, pp. 470–477.

  25. 25

    Ghosh, C. and Iversen, P.L., Antisense Nucleic Acid Drug Dev., 2000, vol. 10, no. 4, pp. 263–274.

  26. 26

    Moulton, H.M., Curr. Pharm. Des., 2013, vol. 19, no. 16, pp. 2963–2969.

  27. 27

    Li, Y.F. and Morcos, P.A., Bioconjugate Chem., 2008, no. 7, pp. 1464–1470.

  28. 28

    Morcos, P.A., Genes, no. 3, pp. 94–102.

  29. 29

    Partridge, M., Vincent, A., Matthews, P., Puma, J., Stein, D., and Summerton, J., Antisense Nucleic Acid Drug Dev., 1996, vol. 6, no. 3, pp. 169–175.

  30. 30

    Kupryushkin, M.S., Pyshnyi, D.V., and Stetsenko, D.A., Acta Naturae, 2014, vol. 6, no. 4, p. 23.

  31. 31

    Stetsenko, D.A., Kupryushkin, M.S., and Pyshnyi, D.V., Modified oligonucleotides and methods for their synthesis, Patent no. WO2016028187A1, 2014.

  32. 32

    Dmitrienko, E., Naumova, O., Fomin, B., Kupryushkin, M., Volkova, A., Amirkhanov, N., Semenov, D., Pyshnaya, I., and Pyshnyi, D., Nanomedicine, 2016, no. 16, pp. 2073–2082.

  33. 33

    Gabriel, G., Nordmann, A., Stein, D.A., Iversen, P.L., and Klenk, H.D., J. Gen. Virol., 2008, vol. 89, pp. 939–948.

  34. 34

    Lenartowicz, E., Nogales, A., Kierzek, E., Kierzek, R., Martinez-Sobrido, L., and Douglas, H., Nucleic Acid Ther., 2016, vol. 26, no. 5, pp. 277–285.

  35. 35

    Vydelenie virusov grippa v kletochnykh kul’turakh i kurinykh embrionakh i ikh identifikatsiya. metodicheskie rekomendatsii (Isolation of Influenza Viruses in Cell Cultures and Chicken Embryos and Their Identification: Guidelines), 2006, no. 0100/4430-06-34.

  36. 36

    Weller, D.D., et al., Oligonucleotide analogs having cationic intersubunit linkages, US Patent no. 7943762 B2, 2011.

Download references

Author information

Correspondence to E. B. Logashenko.

Ethics declarations

No experimentation involving human or animals was part of the present work.

Conflict of Interests

Authors declare that they have no conflict of interest.

Additional information

Translated by E. Martynova

Abbreviations: aON, antisense oligonucleotide; PGO, phosphoryl guanidine oligonucleotide; PMO, morpholino oligonucleotide; PBS, phosphate buffered saline.

A.V. Markov and M.S. Kupryushkin contributed equally to the work.

Corresponding author: phone: +7 (383) 363-51-61; fax: +7 (383) 363-51-53; e-mail:

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Markov, A.V., Kupryushkin, M.S., Goncharova, E.P. et al. Antiviral Activity of a New Class of Chemically Modified Antisense Oligonucleotides against Influenza А Virus. Russ J Bioorg Chem 45, 774–782 (2019) doi:10.1134/S1068162019060268

Download citation


  • influenza virus
  • pandemic influenza A virus (H1N1)
  • antisense oligonucleotides
  • phosphoryl guanidines
  • morpholino oligonucleotides