Potential of application of the RNA interference phenomenon in the treatment of new coronavirus infection COVID-19.

E A Pashkov,V V Zverev,O A Svitich,E B Faizuloev,E R Korchevaya,E P Pashkov,D N Nechaev

doi:10.36233/0507-4088-61

Abstract

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.

Highlights

Potential of application of the RNA interference phenomenon in the treatment of new coronavirus infection COVID-19
COVID-19 has killed more than 4 million people to date and is the most significant global health problem
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)

Summary

REVIEW ARTICLE

For citation: Pashkov E.A., Korchevaya E.R., Faizuloev E.B., Svitich O.A., Pashkov E.P., Nechaev D.N., Zverev V.V. Potential of application of the RNA interference phenomenon in the treatment of new coronavirus infection COVID-19. Возбудитель тяжёлого инфекционного заболевания COVID-19 – коронавирус SARS-CoV-2, относящийся к виду Severe acute respiratory syndrome-related coronavirus рода Betacoronavirus семейства Coronaviridae [2]. Цель данного обзора – оценка потенциала клинического применения малых интерферирующих РНК (миРНК; small interfering RNA, siRNA), направленных на подавление репродукции коронавируса SARSCoV-2, с учётом опыта исследования миРНК в отношении инфекций SARS-CoV и MERS-CoV. Механизм РНК-интерференции заключается в том, что эндонуклеаза Dicer расщепляет чужеродную дцРНК на отдельные двухцепочечные фрагменты длиной до 25 п.н., которые и представляют собой миРНК. Что SARS-CoV, MERS-CoV и SARS-CoV-2 филогенетически близки и относятся к одному роду семейства Coronaviridae, использование механизма РНК-интерференции в подавлении репродукции SARS-CoV-2 может быть весьма многообещающим

Классические подходы к созданию противовирусных препаратов

Альтернативные методики получения противовирусных препаратов

Ссылки References

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