Вопросы вирусологии. 2020; 65: 182-190
Перспектива создания специфических противогриппозных препаратов на основе синтетических малых интерферирующих РНК
https://doi.org/10.36233/0507-4088-2020-65-4-182-190Аннотация
Грипп является одной из самых актуальных проблем здравоохранения во всём мире. Ежегодно гриппом болеют до 15% населения земли, из них около 500 тыс. человек умирают. Особую клиническую значимость представляют вирусы гриппа А и В, имеющие высокий эпидемический и пандемический потенциал. Помимо поражения дыхательных путей, грипп способен вызвать осложнения со стороны сердечно-сосудистой и центральной нервной системы. Несмотря на широкий спектр специфически направленных на различные стадии вирусной репродукции противогриппозных препаратов, наиболее остро стоит проблема формирования вирусной резистентности к традиционным лекарственным препаратам, что требует поиска новых технологий для её преодоления. Перспективным представляется создание лекарственных препаратов, действие которых основано на ингибировании активности вирусных или клеточных генов под влиянием механизмов РНК-интерференции. РНК-интерференция - это каскад регуляторных реакций в эукариотических клетках, вызванный чужеродной экзогенной двухцепочечной РНК, в результате чего происходит расщепление целевой матричной РНК. В настоящем обзоре рассматриваются использование механизма РНК-интер-ференции при разработке специфически направленных противогриппозных средств, а также перспективы, преимущества и недостатки данного подхода. Необходимо учитывать, что важным фактором, снижающим эффективность РНК-интерференции, является формирование резистентности вирусов к действию малых интерферирующих РНК, направленных к вирусным генам. Ввиду этого для преодоления лекарственной устойчивости вируса гриппа наиболее пристального внимания заслуживает исследование применения малых интерферирующих РНК, направленных непосредственно к факторам клетки-хозяина, которые необходимы для репродукции вируса гриппа.
Список литературы
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Problems of Virology. 2020; 65: 182-190
The potential of synthetic small interfering RNA-based antiviral drugs for influenza treatment
https://doi.org/10.36233/0507-4088-2020-65-4-182-190Abstract
Influenza is a worldwide public health problem. Annually, this infection affects up to 15% of the world population; and about half a million people die from this disease every year. Moreover, influenza A and B viruses tend to garner most of the attention, as these types are a major cause of the epidemics and pandemics. Although the influenza virus primarily affects the respiratory tract, it may also affect the cardiovascular and central nervous systems. Several antiviral drugs, that target various stages of viral reproduction, have been considered effective for the treatment and prevention of influenza, but some virus strains become resistant to these medications. Thus, new strategies and techniques should be developed to overcome the antiviral drug resistance. Recent studies suggest that new drugs based on RNA interference (RNAi) appear to be a promising therapeutic approach that regulates the activity of viral or cellular genes. As it is known, the RNAi is a eukaryotic gene regulatory mechanism that can be triggered by a foreign double-stranded RNA (dsRNA) and results in the cleavage of the target messenger RNA (mRNA). This review discusses the prospects, advantages, and disadvantages of using RNAi in carrying out a specific treatment for influenza infection. However, some viruses confer resistance to small interfering RNAs (siRNA) targeting viral genes. This problem can significantly reduce the effectiveness of RNAi. Therefore, applying siRNAs targeting host cell factors required for influenza virus reproduction can be a way to overcome the antiviral drug resistance.
References
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33. Das A.T., Brummelkamp T.R., Westerhout E.M., Vink M., Madire-djo M., Bernards R., et al. Human immunodeficiency virus type 1 escapes from RNA interference-mediated inhibition. J. Virol. 2004; 78(5): 2601-5. DOI: http://doi.org/10.1128/jvi.78.5.2601-2605.2004
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