[Influence of siRNA complexes on the reproduction of influenza A virus (Orthomyxoviridae: Alphainfluenzavirus) in vivo].

INTRODUCTION: Influenza is one of the most pressing global health problems. Despite the wide range of available anti-influenza drugs, the viral drug resistance is an increasing concern and requires the search for new approaches to overcome it. A promising solution is the development of drugs with action that is based on the inhibition of the activity of cellular genes through RNA interference. AIM: Evaluation in vivo of the preventive potential of miRNAs directed to the cellular genes FLT4, Nup98 and Nup205 against influenza infection. MATERIALS AND METHODS: The A/California/7/09 strain of influenza virus (H1N1) and BALB/c mice were used in the study. The administration of siRNA and experimental infection of animals were performed intranasally. The results of the experiment were analyzed using molecular genetic and virological methods. RESULTS: The use of siRNA complexes Nup98.1 and Nup205.1 led to a significant decrease in viral reproduction and concentration of viral RNA on the 3rd day after infection. When two siRNA complexes (Nup98.1 and Nup205.1) were administered simultaneously, a significant decrease in viral titer and concentration of viral RNA was also noted compared with the control groups. CONCLUSIONS: The use of siRNAs in vivo can lead to an antiviral effect when the activity of single or several cellular genes is suppressed. The results indicate that the use of siRNAs targeting the cellular genes whose expression products are involved in viral reproduction is one of the promising methods for the prevention and treatment of not only influenza, but also other respiratory infections.

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

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.

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. 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.

[The potential of synthetic small interfering RNA-based antiviral drugs for influenza treatment].

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.