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Impact of Delivery Method on Antiviral Activity of Phosphodiester, Phosphorothioate, and Phosphoryl Guanidine Oligonucleotides in MDCK Cells Infected with H5N1 Bird Flu Virus Full article

Journal Molecular Biology
ISSN: 0026-8933 , E-ISSN: 1608-3245
Output data Year: 2017, Volume: 51, Number: 4, Pages: 633-638 Pages count : 6 DOI: 10.1134/S0026893317040136
Tags conjugates, influenza A virus, inhibitors, nanoparticles, oligonucleotides, replication
Authors Levina A.S. 1,2 , Repkova M.N. 1,2 , Chelobanov B.P. 1,2 , Bessudnova E.V. 3 , Mazurkova N.A. 4 , Stetsenko D.A. 1 , Zarytova V.F. 1,2
Affiliations
1 Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090 Russia
2 Novosibirsk State University, Novosibirsk, 630090 Russia
3 Institute of Catalysis, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090 Russia
4 Vector State Research Center of Virology and Biotechnology, Koltsovo, Novosibirsk oblast, 630559 Russia

Funding (3)

1 Russian Foundation for Basic Research 15-04-04109
2 Russian Science Foundation 16-15-10073
3 Russian Science Foundation 15-15-00121

Abstract: We have previously described nanocomposites containing conjugates or complexes of native oligodeoxyribonucleotides with poly-L-lysine and TiO2 nanoparticles. We have shown that these nanocomposites efficiently suppressed influenza A virus reproduction in MDCK cells. Here, we have synthesized previously undescribed nanocomposites that consist of TiO2 nanoparticles and polylysine conjugates with oligonucleotides that contain phosphoryl guanidine or phosphorothioate internucleotide groups. These nanocomposites have been shown to exhibit antiviral activity in MDCK cells infected with H5N1 influenza A virus. The nanocomposites containing phosphorothioate oligonucleotides inhibited virus replication ~130-fold. More potent inhibition, i.e., ~5000-fold or ~4600-fold, has been demonstrated by nanocomposites that contain phosphoryl guanidine or phosphodiester oligonucleotides, respectively. Free oligonucleotides have been nearly inactive. The antiviral activity of oligonucleotides of all three types, when delivered by Lipofectamine, has been significantly lower compared to the oligonucleotides delivered in the nanocomposites. In the former case, the phosphoryl guanidine oligonucleotide has appeared to be the most efficient; it has inhibited the virus replication by a factor of 400. The results make it possible to consider phosphoryl guanidine oligonucleotides, along with other oligonucleotide derivatives, as potential antiviral agents against H5N1 avian flu virus.
Cite: Levina A.S. , Repkova M.N. , Chelobanov B.P. , Bessudnova E.V. , Mazurkova N.A. , Stetsenko D.A. , Zarytova V.F.
Impact of Delivery Method on Antiviral Activity of Phosphodiester, Phosphorothioate, and Phosphoryl Guanidine Oligonucleotides in MDCK Cells Infected with H5N1 Bird Flu Virus
Molecular Biology. 2017. V.51. N4. P.633-638. DOI: 10.1134/S0026893317040136 WOS Scopus РИНЦ AN OpenAlex
Original: Левина А.С. , Репкова М.Н. , Челобанов Б.П. , Бессуднова Е.В. , Мазуркова Н.А. , Стеценко Д.А. , Зарытова В.Ф.
Влияние способа доставки на противовирусную активность фосфодиэфирных, тиофосфатных и фосфорилгуанидиновых олигонуклеотидов в клетках MDCK инфицированных вирусом птичьего гриппа A (H5N1)
Молекулярная биология. 2017. Т.51. №4. С.717-723. DOI: 10.7868/S0026898417040139RSCI Scopus РИНЦ OpenAlex
Dates:
Submitted: Jul 5, 2016
Accepted: Oct 15, 2016
Published print: Jul 1, 2017
Published online: Aug 23, 2017
Identifiers:
Web of science: WOS:000408217400020
Scopus: 2-s2.0-85028350458
Elibrary: 31055078
Chemical Abstracts: 2017:1372907
OpenAlex: W4249494374
Citing:
DB Citing
Web of science 5
Scopus 6
Elibrary 5
OpenAlex 8
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