Problems of VirologyProblems of Virology0507-40882411-2097Central Research Institute for Epidemiology67510.36233/0507-4088-159Research ArticleInfluence of siRNA complexes on the reproduction of influenza A virus (Orthomyxoviridae: <i>Alphainfluenzavirus</i>) <i>in vivo</i>PashkovEvgeny A.<p>postgraduate of microbiology, virology and immunology department; junior researcher laboratory of virology applied</p>pashckov.j@yandex.ruhttps://orcid.org/0000-0002-5682-4581MomotViktoriia Y.<p>student of the Institute of Medical Biochemistry</p>momot_v_yu@student.sechenov.ruhttps://orcid.org/0000-0003-3476-5485PakAnastasia V.<p>student of the Institute of Clinical Medicine</p>dcnnpk@gmail.comhttps://orcid.org/0000-0003-4295-7858SamoilikovRoman V.<p>researcher laboratory of molecular immunology</p>roma_sam78@mail.ruhttps://orcid.org/0000-0001-6405-1390PashkovGeorge A.<p>student of the Institute of Children Health</p>georgp2004@mail.ruhttps://orcid.org/0000-0003-0392-9969UsatovaGalina N.<p>Ph. D., private-docent Professor of Microbiology, Virology and Immunology department</p>g.n.usatova@mail.ruhttps://orcid.org/0000-0002-8955-3570KravtsovaElena O.<p>Ph. D., private-docent Professor of Microbiology, Virology and Immunology department</p>elenakravtsov@yandex.ruhttps://orcid.org/0000-0002-9100-0422PoddubikovAlexander V.<p>Ph. D., The Head of laboratory of opportunistic pathogenic bacteria</p>poddubikov@yandex.ruhttps://orcid.org/0000-0001-8962-4765NagievaFiraya G.<p>MD, private-docent, The Head of laboratory of hybrid cell cultures</p>fgn42@yandex.ruhttps://orcid.org/0000-0001-8204-4899SidorovAlexander V.<p>Ph. D., The Head of laboratory of DNA viruses</p>sashasidorov@yandex.ruhttps://orcid.org/0000-0002-3561-8295PashkovEvgeny P.<p>MD, Professor of Microbiology, Virology and Immunology department</p>9153183256@mail.ruhttps://orcid.org/0000-0002-4963-5053SvitichOxana A.<p>Corresponding member of RAS, MD, The head; Professor of Microbiology, Virology and Immunology department</p>svitichoa@yandex.ruhttps://orcid.org/0000-0003-1757-8389ZverevVitaliy V.<p>Academician of RAS, Doctor of Biological Sciences, Scientific Adviser; Professor, The Leader of Microbiology, Virology and Immunology department</p>vitalyzverev@outlook.comhttps://orcid.org/0000-0002-0017-1892Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)I.I. Mechnikov Scientific and Research Institute of Vaccines and Sera180520236829510416012023Copyright © 2023, Pashkov E.A., Momot V.Y., Pak A.V., Samoilikov R.V., Pashkov G.A., Usatova G.N., Kravtsova E.O., Poddubikov A.V., Nagieva F.G., Sidorov A.V., Pashkov E.P., Svitich O.A., Zverev V.V.2023<p><strong>Introduction. </strong>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.</p>
<p><strong>Aim. </strong>Evaluation <em>in vivo</em> of the preventive potential of miRNAs directed to the cellular genes <em>FLT4</em>, <em>Nup98</em> and <em>Nup205 </em>against influenza infection.</p>
<p><strong>Materials and methods. </strong>The A/California/7/09 strain of influenza virus (H<sub>1</sub>N<sub>1</sub>) 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.</p>
<p><strong>Results. </strong>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.</p>
<p><strong>Conclusions.</strong> The use of siRNAs <em>in vivo</em> 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.</p>RNA interferenceinfluenza A virusgene expressionsiRNAviral RNAviral reproductionNup98Nup205РНК-интерференциявирус гриппа Аэкспрессия геновмиРНКвирусная РНКвирусная репродукцияNup98Nup205[WHO. World Health Day 2023. Health For All. Available at: https://www.euro.who.int/ru/media-centre/events/events/2021/10/flu-awareness-campaign-2021][Britannica. 1968 flu pandemic. Global outbreak. Available at: https://www.britannica.com/event/1968-flu-pandemic][Trilla A., Trilla G., Daer C. The 1918 “Spanish flu” in Spain. Clin. Infect. 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