Russian Journal of Infection and ImmunityRussian Journal of Infection and ImmunityИнфекция и иммунитет2220-76192313-7398SPb RAACI15310.15789/2220-7619-2014-1-15-26REVIEWSОБЗОРЫINFLUENCE ON CELLULAR TARGETS FOR TREATING INFLUENZA INFECTIONВОЗДЕЙСТВИЕ НА КЛЕТОЧНЫЕ МИШЕНИ КАК СРЕДСТВО БОРЬБЫ С ГРИППОЗНОЙ ИНФЕКЦИЕЙZarubaevV. V.ЗарубаевВ. В.
Russian Federation

PhD (Biology), Head of the Laboratory of Molecular Anti-Viral Chemotherapy

197376, Russian Federation, St. Petersburg, Professor Popov str., 15/17

к.б.н., зав. лабораторией молекулярных основ химиотерапии вирусных инфекций

197376, Россия, Санкт-Петербург, ул. Профессора Попова, 15/17

zarubaev@influenza.spb.ruSmirnovV. S.СмирновВ. С.
Russian Federation

PhD, MD (Medicine), Principal Scientist, MBRD “Cytomed”, St. Petersburg

д.м.н., главный научный сотрудник

zarubaev@influenza.spb.ruResearch Institute of Influenza, Ministry of Health of the Russian Federation, St. PetersburgФГБУ НИИ гриппа МЗ РФ, Санкт-ПетербургMBRD “Cytomed”, St. PetersburgЗАО МБНПК «Цитомед», Санкт-Петербург090720144115260907201409072014Copyright ©; 2014, Zarubaev V.V., Smirnov V.S.Copyright ©; 2014, Зарубаев В.В., Смирнов В.С.2014Zarubaev V.V., Smirnov V.S.Зарубаев В.В., Смирнов В.С.https://creativecommons.org/licenses/by/4.0https://iimmun.ru/iimm/article/view/153

Аbstract. Influenza is a highly contagious infection of humans. The use of specific antivirals leads to emergence of drug-resistant strains following by the decrease of efficacy of ethiotropic chemotherapy. In this review the data about the decrease of the level of viral replication and severity of pathological process based on the use of alternative targets of cellular instead of viral origin are presented. The medicines for decreasing the production of proinflammatory cytokines (eritoran), restricting the degranulation of mast cells (ketotifen), inhibitors of cyclooxygenases (celexocib, mesalasine, SC-560), inhibitors of sphingosine-1-phospate pathway (AAL-R) and compounds increasing the capillars stability by strengthe ning the contacts between endothelial cells (Slit protein) have been described in the review. The special attention is paid to the inhibitors of cellular pathways that are used by the virus to provide its reproduction, such as NF-κB, Raf/MEK/ERK, PI3K/AKT/mTOR. Information concerning anti-influenza activity of kinase and autophagy inhibitors is summarised as well as data about the preparations of combined mechanism of activity — glycirrhizic acid and dipeptide alpha-glutamyl-tryptophane. Further studies in the field of search and optimization of inhibitors of cellular components as remedies against influenza infection could lead to the development of novel antivirals with high efficacy, broad spectrum of activity and low probability of virus resistance.

Резюме. Грипп представляет собой высоко контагиозное заболевание человека. На фоне использования противовирусных препаратов формируются лекарственно-устойчивые штаммы вируса, следствием чего является снижение эффективности этиотропной химиотерапии. В обзоре рассмотрены способы снижения уровня репликации вируса и тяжести патологического процесса, основанные на использовании альтернативных мишеней не вирусного, а клеточного происхождения. Описаны препараты, снижающие продукцию провоспалительных цитокинов (эриторан), ограничивающие дегрануляцию тучных клеток (кетотифен), ингибиторы циклооксигеназ (целекоксиб, месалазин, SC-560), ингибиторы сфингозин-1-фосфатного пути (AAL-R), а также повышающие стабильность сосудов путем упрочения контактов между эндотелиальными клетками (белок Slit). Особое внимание уделено ингибиторам клеточных путей, используемых вирусом для повышения репродукции, таких как NF-kB, Raf/MEK/ERK, PI3K/AKT/mTOR. Описана противогриппозная активность ингибиторов киназ и процесса аутофагии, а также препаратов смешанного механизма действия — глицирризиновой кислоты и дипептида α-глутамилтриптофана. Дальнейшие исследования в области поиска и оптимизации ингибиторов клеточных компонентов как средств против гриппозной инфекции могут привести к разработке новых противовирусных препаратов высокой эффективности, широкого спектра действия и низкой вероятности развития резистентности.

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