Journal
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY
Volume 45, Issue 6, Pages 774-782Publisher
MAIK NAUKA/INTERPERIODICA/SPRINGER
DOI: 10.1134/S1068162019060268
Keywords
influenza virus; antisense oligonucleotides; phosphoryl guanidines; morpholino oligonucleotides
Funding
- Basic Budget Funding Project of the Basic Research Program of the State Academies of Sciences [AAAA-A17-117020210024-8]
- Russian Science Foundation [19-14-00204]
- Russian Science Foundation [19-14-00204] Funding Source: Russian Science Foundation
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The paper reports the synthesis of a series of antisense oligonucleotides (aONs) directed against different segments of the influenza A virus genome (H1N1) and screening of their antiviral activity in the influenza A virus (H1N1)/MDCK cells and influenza A virus (H1N1)/A549 cells systems. The results of screening have shown that PB1-2AUG-R aON targeted towards the AUG codon region of the segment 2 of virus genome possessed the highest antiviral activity. The synthesized morpholino analog (PMO) and the new phosphoryl guanidine oligodeoxyribonucleotide (PGO) with the sequence of oligonucleotide PB1-2AUG-R provided a comparable biological effects: the influenza virus titer in MDCK cell culture was reduced by 15 times compared to the control when PGO was used in the concentration of 10 mu M and by 40 times when PMO was used in the concentration of 20 mu M. For the delivery of electrically neutral analogs of oligonucleotides (PGO and PMO), the perforation method proposed for PMO was used.
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