Research output: Contribution to journal › Article › peer-review
Impact of Delivery Method on Antiviral Activity of Phosphodiester, Phosphorothioate, and Phosphoryl Guanidine Oligonucleotides in MDCK Cells Infected with H5N1 Bird Flu Virus. / Levina, A. S.; Repkova, M. N.; Chelobanov, B. P. et al.
In: Molekuliarnaia biologiia, Vol. 51, No. 4, 01.07.2017, p. 717-723.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Impact of Delivery Method on Antiviral Activity of Phosphodiester, Phosphorothioate, and Phosphoryl Guanidine Oligonucleotides in MDCK Cells Infected with H5N1 Bird Flu Virus
AU - Levina, A. S.
AU - Repkova, M. N.
AU - Chelobanov, B. P.
AU - Bessudnova, E. V.
AU - Mazurkova, N. A.
AU - Stetsenko, D. A.
AU - Zarytova, V. F.
PY - 2017/7/1
Y1 - 2017/7/1
N2 - 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.
AB - 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.
KW - conjugates
KW - influenza A virus
KW - inhibitors
KW - nanoparticles
KW - oligonucleotides
KW - replication
KW - Animals
KW - Antiviral Agents/chemical synthesis
KW - Dogs
KW - Dose-Response Relationship, Drug
KW - Drug Carriers
KW - Guanidines/chemistry
KW - Influenza A Virus, H5N1 Subtype/drug effects
KW - Lipids/chemistry
KW - Madin Darby Canine Kidney Cells
KW - Nanocomposites/chemistry
KW - Oligonucleotides/chemistry
KW - Organophosphates/chemistry
KW - Phosphorothioate Oligonucleotides/chemistry
KW - Polylysine/chemistry
KW - Titanium/chemistry
KW - Virus Replication/drug effects
UR - http://www.scopus.com/inward/record.url?scp=85044180773&partnerID=8YFLogxK
U2 - 10.7868/S0026898417040139
DO - 10.7868/S0026898417040139
M3 - Article
C2 - 28900092
AN - SCOPUS:85044180773
VL - 51
SP - 717
EP - 723
JO - Molekulyarnaya Biologiya
JF - Molekulyarnaya Biologiya
SN - 0026-8984
IS - 4
ER -
ID: 12178703