Вопросы вирусологии. 2021; 66: 241-251
Потенциал применения явления РНК-интерференции в терапии новой коронавирусной инфекции COVID-1
https://doi.org/10.36233/0507-4088-61Аннотация
Новая коронавирусная инфекция на сегодняшний день привела к гибели свыше 4 млн человек и представляет собой наиболее значимую проблему мирового здравоохранения. Первый зафиксированный случай COVID-19 отмечен в Китайской Народной Республике (КНР) (г. Ухань) в декабре 2019 г., а уже 11 марта 2020 г. Всемирная организация здравоохранения (ВОЗ) объявила пандемию в связи с быстрым распространением этой инфекции. Помимо поражения органов дыхания её возбудитель SARS-CoV-2 способен вызывать тяжёлые осложнения, которые могут затронуть практически все системы организма. В связи с недостаточной эффективностью терапии COVID-19 сохраняется острая необходимость в разработке эффективных специфических лекарственных средств. Среди известных подходов к созданию противовирусных препаратов весьма перспективным направлением является получение соединений, действие которых опосредовано механизмом РНК-интерференции. РНК-интерференция – регуляторный путь, при котором молекула малой интерферирующей РНК (миРНК; small interfering RNA, siRNA) подавляет экспрессию гена-мишени. Это явление позволяет быстро создать целую серию высокоэффективных противовирусных веществ при условии, что известна только последовательность матричной РНК (мРНК, mRNA) целевого вирусного бел[1]ка. В настоящем обзоре рассматривается возможность клинического применения миРНК, направленных
на подавление репродукции нового коронавируса SARS-CoV-2, с учётом опыта подобных исследований на моделях инфицирования SARS-CoV и MERS-CoV. Важно помнить, что эффективность использования молекул миРНК, нацеленных на вирусные гены, может снизиться из-за формирования к ним устойчивости патогена. В связи с этим особого внимания заслуживает дизайн миРНК, нацеленных на клеточные факторы, необходимые для репродукции SARS-CoV-2.
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Problems of Virology. 2021; 66: 241-251
Potential of application of the RNA interference phenomenon in the treatment of new coronavirus infection COVID-19
https://doi.org/10.36233/0507-4088-61Abstract
COVID-19 has killed more than 4 million people to date and is the most significant global health problem. The first recorded case of COVID-19 had been noted in Wuhan, China in December 2019, and already on March 11, 2020, World Health Organization declared a pandemic due to the rapid spread of this infection. In addition to the damage to the respiratory system, SARS-CoV-2 is capable of causing severe complications that can affect almost all organ systems. Due to the insufficient effectiveness of the COVID-19 therapy, there is an urgent need to develop effective specific medicines. Among the known approaches to the creation of antiviral drugs, a very promising direction is the development of drugs whose action is mediated by the mechanism of RNA interference (RNAi). A small interfering RNA (siRNA) molecule suppresses the expression of a target gene in this regulatory pathway. The phenomenon of RNAi makes it possible to quickly create a whole series of highly effective antiviral drugs, if the matrix RNA (mRNA) sequence of the target viral protein is known. This review examines the possibility of clinical application of siRNAs aimed at suppressing reproduction of the SARS-CoV-2, taking into account the experience of similar studies using SARS-CoV and MERS-CoV infection models. It is important to remember that the effectiveness of siRNA molecules targeting viral genes may decrease due to the formation of viral resistance. In this regard, the design of siRNAs targeting the cellular factors necessary for the reproduction of SARS-CoV-2 deserves special attention.
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