Перспектива применения препаратов на основе явления РНК-интерференции против ВИЧ-инфекции

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Вопросы вирусологии. 2022; 67: 278-289

Перспектива применения препаратов на основе явления РНК-интерференции против ВИЧ-инфекции

Пашков Е. А., Пак А. В., Пашков Е. П., Быков А. С., Буданова Е. В., Поддубиков А. В., Свитич О. А., Зверев В. В.

https://doi.org/10.36233/0507-4088-124

Аннотация

На сегодняшний день вирус иммунодефицита человека (ВИЧ, HIV) является одной из наиболее актуальных проблем мирового здравоохранения. С момента открытия в 1978 г. он унёс жизни более 35 млн человек, а число инфицированных сегодня достигает 37 млн человек. При отсутствии высокоактивной антиретровирусной терапии ВИЧ-инфекция характеризуется неуклонным снижением количества CD4⁺ Т-лимфоцитов, однако её проявления способны затронуть центральную нервную, сердечно-сосудистую, пищеварительную, эндокринную и мочеполовую системы. Одновременно с этим особую опасность представляют осложнения, индуцированные представителями патогенной и условно-патогенной микрофлоры, которые могут привести к развитию сопутствующих бактериальных, грибковых и вирусных инфекций. Следует учитывать, что важной проблемой является возникновение вирусов, устойчивых к традиционным лекарственным препаратам, а также токсичность самих лекарственных средств для организма. В контексте настоящего обзора особый интерес представляет оценка перспективности создания и клинического применения препаратов на основе малых интерферирующих РНК, направленных на подавление репродукции ВИЧ, с учётом опыта подобных исследований, проведённых ранее. РНК-интерференция – каскад регуляторных реакций в эукариотических клетках, в результате которого происходит деградация чужеродной матричной РНК. Разработка препаратов на основе механизма РНК-интерференции позволит преодолеть проблему вирусной резистентности. Наряду с этим данная технология позволяет оперативно реагировать на случаи возникновения вспышек новых вирусных заболеваний.

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Problems of Virology. 2022; 67: 278-289

The prospects for the use of drugs based on the phenomenon of RNA interference against HIV infection

Pashkov E. A., Pak A. V., Pashkov E. P., Bykov A. S., Budanova E. V., Poddubikov A. V., Svitich O. A., Zverev V. V.

https://doi.org/10.36233/0507-4088-124

Abstract

The human immunodeficiency virus (HIV) is currently one of the most pressing global health problems. Since its discovery in 1978, HIV has claimed the lives of more than 35 million people, and the number of people infected today reaches 37 million. In the absence of highly active antiretroviral therapy (HAART), HIV infection is characterized by a steady decrease in the number of CD4⁺ T-lymphocytes, but its manifestations can affect the central nervous, cardiovascular, digestive, endocrine and genitourinary systems. At the same time, complications induced by representatives of pathogenic and opportunistic microflora, which can lead to the development of bacterial, fungal and viral concomitant infections, are of particular danger. It should be borne in mind that an important problem is the emergence of viruses resistant to standard therapy, as well as the toxicity of the drugs themselves for the body. In the context of this review, of particular interest is the assessment of the prospects for the creation and clinical use of drugs based on small interfering RNAs aimed at suppressing the reproduction of HIV, taking into account the experience of similar studies conducted earlier. RNA interference is a cascade of regulatory reactions in eukaryotic cells, which results in the degradation of foreign messenger RNA. The development of drugs based on the mechanism of RNA interference will overcome the problem of viral resistance. Along with this, this technology makes it possible to quickly respond to outbreaks of new viral diseases.

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