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


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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 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.

作者简介

A. Markov

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences

Email: evg_log@niboch.nsc.ru
俄罗斯联邦, Novosibirsk, 630090

M. Kupryushkin

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences

Email: evg_log@niboch.nsc.ru
俄罗斯联邦, Novosibirsk, 630090

E. Goncharova

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences

Email: evg_log@niboch.nsc.ru
俄罗斯联邦, Novosibirsk, 630090

R. Amirkhanov

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences

Email: evg_log@niboch.nsc.ru
俄罗斯联邦, Novosibirsk, 630090

S. Vasilyeva

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences

Email: evg_log@niboch.nsc.ru
俄罗斯联邦, Novosibirsk, 630090

D. Pyshnyi

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences

Email: evg_log@niboch.nsc.ru
俄罗斯联邦, Novosibirsk, 630090

M. Zenkova

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences

Email: evg_log@niboch.nsc.ru
俄罗斯联邦, Novosibirsk, 630090

E. Logashenko

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences

编辑信件的主要联系方式.
Email: evg_log@niboch.nsc.ru
俄罗斯联邦, Novosibirsk, 630090

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