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Vol 51(2017) N 4 p. 633-638; DOI 10.1134/S0026893317040136 Full Text

A.S. Levina1,2, M.N. Repkova1,2, B.P. Chelobanov1,2, E.V. Bessudnova3, N.A. Mazurkova4, D.A. Stetsenko1, V.F. Zarytova1,2*

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

1Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090 Russia
2Novosibirsk State University, Novosibirsk, 630090 Russia
3Institute of Catalysis, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090 Russia
4Vector State Research Center of Virology and Biotechnology, Koltsovo, Novosibirsk oblast, 630559 Russia

*Zarytova@niboch.nsc.ru
Received - 2016-07-05; Accepted - 2016-10-15

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.

oligonucleotides, conjugates, nanoparticles, influenza A virus, replication, inhibitors



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