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

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Abstract

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.

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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: evg_log@niboch.nsc.ru.

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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

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Keywords:

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