vestnik-bio-msuВестник Московского университета. Серия 16. БиологияVestnik Moskovskogo universiteta. Seriya 16. Biologiya0137-0952Lomonosov Moscow State University, School of Biology10.55959/MSU0137-0952-16-79-4-14vestnik-bio-msu-1442Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯRESEARCH ARTICLESЭффективное ингибирование репликации вируса простого герпеса 1-го типа in vitro с помощью олигонуклеотид-содержащих нанокомпозитовEffective in vitro inhibition of herpes simplex virus type 1 replication by oligonucleotide-containing nanocompositeshttps://orcid.org/0000-0002-7108-9036РепковаМ. Н.RepkovaM. N.

Репкова Марина Николаевна – канд. хим. наук, науч. сотр.  

630090, г. Новосибирск, пр. Лаврентьева, д. 8, Тел.: 8-383-363-51-23 

8 Lavrent’eva pr., Novosibirsk, 630090 

repk56@mail.ruhttps://orcid.org/0000-0002-9579-9972ЗарытоваВ. Ф.ZarytovaV. F.

Зарытова Валентина Филипповна – докт. хим. наук, гл. науч. сотр. 

630090, г. Новосибирск, пр. Лаврентьева, д. 8, Тел.: 8-383-363-51-23

8 Lavrent’eva pr., Novosibirsk, 630090 

zarytova@niboch.nsc.ruhttps://orcid.org/0000-0001-8164-4091МазурковО. Ю.MazurkovO. Yu.

Мазурков Олег Юрьевич – канд. биол. наук, науч. сотр.  

Новосибирская область, 630559, Кольцово, Тел.: 8-383-363-47-00

Koltsovo, Novosibirsk region, 630559 

mazurkov_oleg@mail.ruhttps://orcid.org/0000-0002-1896-2684МазурковаН. А.MazurkovaN. A.

Мазуркова Наталья Алексеевна – докт. биол. наук, зав. лаб.

Новосибирская область, 630559, Кольцово, Тел. 8-383-363-47-00 

Koltsovo, Novosibirsk region, 630559 

mazurkova@vector.nsc.ruhttps://orcid.org/0000-0002-5146-8979МакаревичЕ. В.MakarevichE. V.

Макаревич Елена Викторовна – канд. биол. наук, науч. сотр. 

Новосибирская область, 630559, Кольцово, Тел.: 8-383-363-47-00  

Koltsovo, Novosibirsk region, 630559 

elenasazmakarevich@yandex.ruhttps://orcid.org/0000-0001-9554-4462ФилипповаЕ. И.FilippovaE. I.

Филиппова Екатерина Игоревна – канд. биол. наук, науч. сотр. 

Новосибирская область, 630559, Кольцово, Тел.: 8-383-363-47-00 

Koltsovo, Novosibirsk region, 630559 

filippova.ekaterina.89@gmail.comhttps://orcid.org/0000-0002-6510-499XНекрасовМ. Д.NekrasovM. D.

Некрасов Михаил Дмитриевич – науч. сотр. 

630090, г. Новосибирск, пр. Лаврентьева, д. 8, Тел.: 8-383-363-51-23 

8 Lavrent’eva pr., Novosibirsk, 630090 

shuenja@gmail.comhttps://orcid.org/0000-0002-2300-7809КупрюшкинМ. С.KupryushkinM. S.

Купрюшкин Максим Сергеевич – канд. хим. наук, ст. науч. сотр. 

630090, г. Новосибирск, пр. Лаврентьева, д. 8, Тел.: 8-383-363-51-23

8 Lavrent’eva pr., Novosibirsk, 630090 

kuprummax@niboch.nsc.ruhttps://orcid.org/0000-0003-2423-3805ЛевинаА. С.LevinaA. S.

Левина Ася Сауловна – канд. хим. наук, ст. науч. сотр. 

630090, г. Новосибирск, пр. Лаврентьева, д. 8, Тел.: 8-383-363-51-23 

8 Lavrent’eva pr., Novosibirsk, 630090 

asl1032@yandex.ruИнститут химической биологии и фундаментальной медицины, Сибирское отделение Российской академии наукРоссияInstitute of Chemical Biology and Fundamental Medicine, Siberian Brunch of Russian Academy of SciencesRussian FederationГосударственный научный центр вирусологии и биотехнологии «Вектор»РоссияState Research Center of Virology and Biotechnology “Vector”Russian Federation202403032025794338345Copyright © Репкова М.Н., Зарытова В.Ф., Мазурков О.Ю., Мазуркова Н.А., Макаревич Е.В., Филиппова Е.И., Некрасов М.Д., Купрюшкин М.С., Левина А.С., 20252025Репкова М.Н., Зарытова В.Ф., Мазурков О.Ю., Мазуркова Н.А., Макаревич Е.В., Филиппова Е.И., Некрасов М.Д., Купрюшкин М.С., Левина А.С.Repkova M.N., Zarytova V.F., Mazurkov O.Y., Mazurkova N.A., Makarevich E.V., Filippova E.I., Nekrasov M.D., Kupryushkin M.S., Levina A.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestnik-bio-msu.elpub.ru/jour/article/view/1442

Борьба с герпесвирусными инфекциями является насущной проблемой общественного здравоохранения из-за широкой распространенности вируса простого герпеса, который вызывает целый ряд заболеваний, начиная от легких первичных поражений кожи и заканчивая тяжелым, а иногда и смертельным энцефалитом. Использование антисмысловых олигонуклеотидов (ON, oligonucleotide) для подавления репликации вируса простого герпеса является многообещающим направлением в этой области. Для доставки ON в клетки мы создали нанокомпозиты, состоящие из антисмысловых ON, иммобилизованных на наночастицах TiO2 в форме анатаза (Ans~ON). Мы исследовали противовирусную активность нескольких нанокомпозитов, содержащих ON, нацеленные на различные участки генома вируса простого герпеса 1. В работе использовались немодифицированные ON и ON с метилсульфонилфосфорамидными межнуклеотидными группами. Наиболее эффективные нанокомпозиты снижали репликацию вируса в культуре клеток на 3–3,5 порядка. Значения индекса селективности этих нанокомпозитов были оценены как 90–110 в лечебном режиме.

The control of herpesvirus infections is a pressing public health issue because of the widespread prevalence of herpes simplex virus (HSV), which causes a variety of diseases ranging from mild primary skin lesions to severe and sometimes fatal encephalitis. The use of antisense oligonucleotides (ONs) to suppress HSV replication is a promising development in this field. To overcome one of the major obstacles in delivering ONs into cells, we have prepared nanocomposites, which are composed of antisense oligonucleotides immobilized on titanium dioxide nanoparticles in the form of anatase (Ans~ON). We have investigated the antiviral activity of several nanocomposites bearing oligonucleotides targeting different regions of the HSV-1 genome. Unmodified oligonucleotides and oligonucleotides with methylsulfonyl phosphoramidate internucleotide groups have been used in the work. The most effective nanocomposites reduced virus replication in the cell culture by 3–3.5 orders of magnitude. The selectivity index values of these nanocomposites have been evaluated as 90–110 in the postinfection mode.

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