The Impact of Delivery Method on Antiviral Activity of Phosphodiester, Phosphorothioate and Phosphoryl Guanidine Oligonucleotides in MDCK Cells Infected by Avian Influenza A Virus H5N1
We have previously described the application of nanocomposites containing conjugates of native oligodeoxy-ribonucleotides with poly-L-lysine and TiO<sub>2</sub> nanoparticles for cellular delivery of oligonucleotides. It was shown that these nanocomposites efficiently suppressed influenza A virus reproduction in MDCK cells. Herein we described the nanocomposites containing oligonucleotides with phosphoryl guanidine or phos-phorothioate internucleotide groups that similarly to their phosphodiester counterparts exhibited potent antiviral activity in MDCK cells infected with influenza A virus H5N1. Nanocomposite containing phosphorothioate oligonucleotide inhibited virus reproduction ~130 times, whereas much higher activity (~5000 times and ~4600 times) was demonstrated by those containing phosphoryl guanidine or phosphodiester oligonucle-otide, respectively. Free oligonucleotides were nearly inactive. When delivered by Lipofectamine, the activity of all three types of oligonucleotides was much lower: the best inhibition (~400 times) was shown by phosphoryl guanidine oligonucleotide. The results open the possibility of future application of phosphoryl guan-idine oligonucleotides as potential antiviral agents against the influenza A virus H5N1 along with other oli-gonucleotide derivatives.