ecodagЮг России: экология, развитиеSouth of Russia: ecology, development1992-10982413-0958State Institute of Applied Ecology of the Republic of Dagestan10.18470/1991-1098-2026-1-1ecodag-3639Research ArticleВИРУСОЛОГИЯVIROLOGYПротивовирусная активность комбинаций антисмысловых олигонуклеотидов, направленных на различные области генома ВИЧ‐1Antiviral activity of antisense oligonucleotide combinations targeting various regions of the HIV‐1 genomehttps://orcid.org/0000-0001-5896-8231ГотфридЛ. Г.GotfridL. G.

Людмила Г. Готфрид - н.с.

630559 рп. Кольцово, Новосибирская область. Тел. +79134506795

Ludmila G. Gotfrid - Researcher.

Koltsovo, Novosibirsk region, 630559, Tel. +79134506795

gotfrid_lg@vector.nsc.ruhttps://orcid.org/0000-0002-2300-7809КупрюшкинМ. С.KupryushkinM. S.

Максим С. Купрюшкин

Новосибирск

Maxim S. Kupryushkin

Novosibirsk

https://orcid.org/0000-0001-7889-6319ПавловаА. С.PavlovaA. S.

Анна С. Павлова

Новосибирск

Anna S. Pavlova

Novosibirsk

https://orcid.org/0000-0001-9888-5422ГашниковаМ. П.GashnikovaM. P.

Мария П. Гашникова

Кольцово

Maria P. Gashnikova

Koltsovo

https://orcid.org/0000-0002-7418-4872ТотменинА. В.TotmeninA. V.

Алексей В. Тотменин

Кольцово

Alexei V. Totmenin

Koltsovo

https://orcid.org/0000-0002-7559-2376ПышнаяИ. А.PyshnayaI. A.

Инна А. Пышная

Новосибирск

Inna A. Pyshnaya

Novosibirsk

https://orcid.org/0000-0002-0891-0880ГашниковаН. М.GashnikovaN. M.

Наталья М. Гашникова

Кольцово

Natalya M. Gashnikova

Koltsovo

ФБУН ГНЦ ВБ «Вектор» РоспотребнадзораVector State Research Centre of Virology and Biotechnology, RospotrebnadzorИнститут химической биологии и фундаментальной медицины СО РАНInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences2026130520262116‐13Copyright © Готфрид Л.Г., Купрюшкин М.С., Павлова А.С., Гашникова М.П., Тотменин А.В., Пышная И.А., Гашникова Н.М., 20262026Готфрид Л.Г., Купрюшкин М.С., Павлова А.С., Гашникова М.П., Тотменин А.В., Пышная И.А., Гашникова Н.М.Gotfrid L.G., Kupryushkin M.S., Pavlova A.S., Gashnikova M.P., Totmenin A.V., Pyshnaya I.A., Gashnikova N.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://ecodag.elpub.ru/ugro/article/view/3639

Цель – исследовать способность комбинаций антисмысловых тиофосфатных олигодезоксирибонуклеотидов, направленных на консервативные участки генома ВИЧ‐1, подавлять репродукцию вируса.

Антиретровирусную активность антисмысловых олигонуклеотидов исследовали на лимфоидной культуре клеток человека МТ4, инфицированной штаммом ВИЧ‐1 суб‐субтипа А6, путем определения количества вирусного белка р24 методом иммуноферментного анализа (ИФА).

Изученные олигонуклеотиды и их комбинации продемонстрировали способность подавлять репликацию ВИЧ‐1 в наномолярных концентрациях. Для моно‐олигонуклеотидов наилучшим противовирусным подавлением обладал олигонуклеотид, направленный на область гена gag (IC50=58 ± 4,4 нМ). Среди исследованных комбинаций наилучший показатель IC50 (29 ± 1,7 нМ) был получен для купажа олигонуклеотидов, направленных на области гена gag и праймер‐связывающего сайта, выполненное исследование подтвердило способность комбинаций олигонуклеотидов, направленных на подавление различных участков генома, отвечающих за разные этапы жизненного цикла вируса, синергически усиливать противовирусный эффект по сравнению с эффектом от применения соответствующих олигонуклеотидов по одному. Обоснование возможности использования комбинации олигонуклеотидов имеет большое значение, так как разнонаправленность противовирусного действия олигонуклеотидов позволяет минимизировать возможное негативное влияние мутационной изменчивости ВИЧ на противовирусную эффективность препаратов.

The goal of this study was to investigate the effectiveness in suppressing viral replication of combinations of antisense phosphorothioate oligodeoxyribonucleotides targeting conserved regions in the HIV‐1 genome.

The antiretroviral activity of the antisense oligonucleotides was evaluated using human MT4 lymphocyte culture infected with HIV‐1 subtype A6. The amount of viral protein p24 was measured using an enzyme immunoassay (ELISA) to determine the effectiveness of the oligonucleotides treatments.The oligonucleotides studied and their combinations showed the ability to inhibit HIV‐1 replication at nanomolar concentrations. Among the mono‐oligonucleotides, the one targeting the gag gene region had the best anti‐viral suppression (IC50 = 58 ± 4.4 nM). Among the combinations, the most effective (IC50 = 29 ± 1.7 nM) consisted of oligonucleotides targeting the gag region and the primer binding site. These results confirm the potential of combining oligonucleotides that target different regions of the HIV‐1 genome to synergistically increase the anti‐viral effect, as compared to using each oligonucleotide individually. The justification for using a combination of oligonucleotides is important because the multidirectional antiviral effect of these molecules minimises the potential negative impact of HIV's mutational variability on the effectiveness of antiviral drugs.

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The authors declare that there are no conflicts of interest present.