Antiviral Activity of a New Class of Chemically Modified Antisense Oligonucleotides against Influenza А Virus

— 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 resu...

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Veröffentlicht in:Russian journal of bioorganic chemistry 2019-11, Vol.45 (6), p.774-782
Hauptverfasser: Markov, A. V., Kupryushkin, M. S., Goncharova, E. P., Amirkhanov, R. N., Vasilyeva, S. V., Pyshnyi, D. V., Zenkova, M. A., Logashenko, E. B.
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container_issue 6
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container_title Russian journal of bioorganic chemistry
container_volume 45
creator Markov, A. V.
Kupryushkin, M. S.
Goncharova, E. P.
Amirkhanov, R. N.
Vasilyeva, S. V.
Pyshnyi, D. V.
Zenkova, M. A.
Logashenko, E. B.
description — 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 µM and by 40 times when PMO was used in the concentration of 20 µM. For the delivery of electrically neutral analogs of oligonucleotides (PGO and PMO), the perforation method proposed for PMO was used.
doi_str_mv 10.1134/S1068162019060268
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V. ; Kupryushkin, M. S. ; Goncharova, E. P. ; Amirkhanov, R. N. ; Vasilyeva, S. V. ; Pyshnyi, D. V. ; Zenkova, M. A. ; Logashenko, E. B.</creator><creatorcontrib>Markov, A. V. ; Kupryushkin, M. S. ; Goncharova, E. P. ; Amirkhanov, R. N. ; Vasilyeva, S. V. ; Pyshnyi, D. V. ; Zenkova, M. A. ; Logashenko, E. B.</creatorcontrib><description>— 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 µM and by 40 times when PMO was used in the concentration of 20 µM. 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subjects Biochemistry
Biological effects
Biomedical and Life Sciences
Biomedicine
Bioorganic Chemistry
Genomes
Influenza
Life Sciences
Oligonucleotides
Organic Chemistry
Screening
Viruses
title Antiviral Activity of a New Class of Chemically Modified Antisense Oligonucleotides against Influenza А Virus
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