Antiviral Activity of a New Class of Chemically Modified Antisense Oligonucleotides against Influenza А Virus
- Authors: Markov A.V.1, Kupryushkin M.S.1, Goncharova E.P.1, Amirkhanov R.N.1, Vasilyeva S.V.1, Pyshnyi D.V.1, Zenkova M.A.1, Logashenko E.B.1
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Affiliations:
- Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences
- Issue: Vol 45, No 6 (2019)
- Pages: 774-782
- Section: Article
- URL: https://journals.rcsi.science/1068-1620/article/view/229339
- DOI: https://doi.org/10.1134/S1068162019060268
- ID: 229339
Cite item
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.
About the authors
A. V. Markov
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences
Email: evg_log@niboch.nsc.ru
Russian Federation, Novosibirsk, 630090
M. S. Kupryushkin
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences
Email: evg_log@niboch.nsc.ru
Russian Federation, Novosibirsk, 630090
E. P. Goncharova
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences
Email: evg_log@niboch.nsc.ru
Russian Federation, Novosibirsk, 630090
R. N. Amirkhanov
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences
Email: evg_log@niboch.nsc.ru
Russian Federation, Novosibirsk, 630090
S. V. Vasilyeva
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences
Email: evg_log@niboch.nsc.ru
Russian Federation, Novosibirsk, 630090
D. V. Pyshnyi
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences
Email: evg_log@niboch.nsc.ru
Russian Federation, Novosibirsk, 630090
M. A. Zenkova
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences
Email: evg_log@niboch.nsc.ru
Russian Federation, Novosibirsk, 630090
E. B. Logashenko
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences
Author for correspondence.
Email: evg_log@niboch.nsc.ru
Russian Federation, Novosibirsk, 630090