Impact of delivery method on antiviral activity of phosphodiester, phosphorothioate, and phosphoryl guanidine oligonucleotides in MDCK cells infected with H5N1 bird flu virus

A. S. Levina, M. N. Repkova, B. P. Chelobanov, E. V. Bessudnova, N. A. Mazurkova, D. A. Stetsenko, V. F. Zarytova

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)633-638
Number of pages6
JournalMolecular Biology
Volume51
Issue number4
DOIs
Publication statusPublished - 1 Jul 2017

Keywords

  • conjugates
  • influenza A virus
  • inhibitors
  • nanoparticles
  • oligonucleotides
  • replication
  • ANTISENSE
  • CULTURE
  • NANOPARTICLES
  • NANOCOMPOSITES
  • REPLICATION
  • INFLUENZA-A VIRUS
  • REGIONS

Fingerprint

Dive into the research topics of 'Impact of delivery method on antiviral activity of phosphodiester, phosphorothioate, and phosphoryl guanidine oligonucleotides in MDCK cells infected with H5N1 bird flu virus'. Together they form a unique fingerprint.

Cite this