antibioticsАнтибиотики и ХимиотерапияAntibiot Khimioter = Antibiotics and Chemotherapy0235-2990ООО «Издательство ОКИ»10.37489/0235-2990-2025-70-3-4-69-83ROVYIRantibiotics-1240Research ArticleОБЗОРЫREVIEWSПерспективные направления развития химиотерапии вирусных инфекцийPromising Directions for the Development of Chemotherapy for Viral Infectionshttps://orcid.org/0000-0001-6732-8404ЛогиноваС. Я.LoginovaS. Ya.

Логинова Светлана Яковлевна — д. б. н., ведущий научный сотрудник

Сергиев Посад

Svetlana Ya. Loginova — D. Sc. in Biology, Leading Researcher, 48th Central Scientific Research Institute of the Ministry of Defense of the Russian Federation

Sergiev Posad

https://orcid.org/0000-0002-6742-3919БорисевичС. В.BorisevichS. V.

Борисевич Сергей Владимирович — д. б. н., профессор, академик РАН, начальник

Сергиев Посад

Sergey V. Borisevich — D. Sc. in Biology, Professor, Academician of the Russian Academy of Sciences, Head of the 48th Central Scientific Research Institute of the Ministry of Defense of the Russian Federation

Sergiev Posad

48cnii@mil.ruhttps://orcid.org/0000-0002-5461-3641ЩукинаВ. Н.ShсhukinaV. N.

Щукина Вероника Николаевна — к. б. н., научный сотрудник

Сергиев Посад

Veronika N. Shchukina — Ph. D. in Biology, Researcher, 48th Central Scientific Research Institute of the Ministry of Defense of the Russian Federation

Sergiev Posad 

https://orcid.org/0000-0002-5175-916XСавенкоС. В.SavenkoS. V.

Савенко Сергей Вадимович — старший научный сотрудник

Сергиев Посад

Sergey V. Savenko — Senior Researcher, 48th Central Scientific Research Institute of the Ministry of Defense of the Russian Federation

Sergiev Posad

https://orcid.org/0000-0003-4387-0367РубцовВ. В.RubtsovV. V.

Рубцов Владимир Васильевич — к. вет. н., научный сотрудник

Сергиев Посад

Vladimir V. Rubtsov — Ph. D. Veterinary Sciences, Researcher, 48th Central Scientific Research Institute of the Ministry of Defense of the Russian Federation

Sergiev Posad

ФГБУ «48 ЦНИИ» Минобороны России»Россия48th Central Scientific Research Institute of the Ministry of Defense of the Russian FederationRussian Federation202506082025703-46983Copyright © Логинова С.Я., Борисевич С.В., Щукина В.Н., Савенко С.В., Рубцов В.В., 20252025Логинова С.Я., Борисевич С.В., Щукина В.Н., Савенко С.В., Рубцов В.В.Loginova S.Y., Borisevich S.V., Shсhukina V.N., Savenko S.V., Rubtsov V.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.antibiotics-chemotherapy.ru/jour/article/view/1240

Вирусные инфекции занимают ведущее место в разнообразной патологии человека и являются одной из основных причин смертности среди людей как в развитых, так и развивающихся странах со слабой системой здравоохранения. Огромное разнообразие вирусов и их уникальная изменчивость ставит серьёзную задачу перед разработчиками противовирусных средств. Цель обзора — анализ современного состояния разработки средств экстренной профилактики и лечения, и перспективных направлений развития химиотерапии вирусных инфекций. Основным направлением в разработке эффективных средств для терапии вирусных инфекций является создание препаратов, основанных на аномальных нуклеозидах и их предшественниках, малых интерферирующих РНК, релиз-активных соединений, поиск мишеней среди вирусных белков. В обзоре рассмотрены наиболее значимые результаты в области создания средств терапии вирусных инфекций.

Viral infections occupy a leading place in various human pathologies and are one of the main causes of death among people, both in developed and developing countries with a weak health care system. The huge diversity of viruses and their unique variability pose a serious challenge to the developers of antiviral agents. The purpose of this review is to analyze the current state of development of emergency prevention and treatment agents, as well as promising areas for the development of chemotherapy for viral infections. The main direction in the development of effective means for the treatment of viral infections is the creation of medications based on abnormal nucleosides and their precursors, small interfering RNA, releaseactive compounds, and the search for targets among viral proteins. The review considers the most significant results in the field of creating agents for the treatment of viral infections.

вирусные инфекциианомальные нуклеозидырелиз-активные веществапрепараты широкого спектра действияРНК интерференцияviral infectionsabnormal nucleosidesrelease-active substancesbroad-spectrum drugsRNA interferenceThe authors declare no conflict of interest.ReferencesMühlemann B., Vinner L., Margaryan A. et al. Diverse variola virus (smallpox) strains were widespread in northern Europe in the Viking AgeЮ Science. 2020; 369 (6502): eaaw 8977. doi: 10.1126/science.aaw8977.Mühlemann B., Vinner L., Margaryan A. et al. Diverse variola virus (smallpox) strains were widespread in northern Europe in the Viking AgeЮ Science. 2020; 369 (6502): eaaw 8977. doi: 10.1126/science.aaw8977.Basler C. F. Influenza viruses: Basic biology and potential drug targets. Infect Disord Drug Targets. 2007; 7: 282–293. doi: 10.2174/187152607783018745.Basler C. F. Influenza viruses: Basic biology and potential drug targets. Infect Disord Drug Targets. 2007; 7: 282–293. doi: 10.2174/187152607783018745.Furuyama W., Marzi A. Ebola virus: pathogenesis and countermeasure development. Annu Rev Virol. 2019; 6: 435–458. doi: 10.1146/annurevvirology-092818-015708.Furuyama W., Marzi A. Ebola virus: pathogenesis and countermeasure development. Annu Rev Virol. 2019; 6: 435–458. doi: 10.1146/annurevvirology-092818-015708.Dyall J., Gross R., Kindrachuk J. et al. Middle East respiratory syndrome and severe acute respiratory syndrome: Current therapeutic options and potential targets for novel therapies. Drugs. 2017; 77: 1935–1966. doi: 10.1007/s40265-017-0830-1.Dyall J., Gross R., Kindrachuk J. et al. Middle East respiratory syndrome and severe acute respiratory syndrome: Current therapeutic options and potential targets for novel therapies. Drugs. 2017; 77: 1935–1966. doi: 10.1007/s40265-017-0830-1.Millet J. K., Whittaker G. R. Host cell proteases: critical determinants of coronavirus tropism and pathogenesis. Virus Res. 2015; 202: 120–134. doi: 10.1016/j.virusres.2014.11.021.Millet J. K., Whittaker G. R. Host cell proteases: critical determinants of coronavirus tropism and pathogenesis. Virus Res. 2015; 202: 120–134. doi: 10.1016/j.virusres.2014.11.021.Ling R., Dai Y., Huang B., Huang W., Yu J., Lu X., Jiang Y. In silico design of antiviral peptides targeting the spike protein of SARS-CoV-2. Peptides. 2020; 130: 170328. doi: 10.1016/j.peptides.2020.170328.Ling R., Dai Y., Huang B., Huang W., Yu J., Lu X., Jiang Y. In silico design of antiviral peptides targeting the spike protein of SARS-CoV-2. Peptides. 2020; 130: 170328. doi: 10.1016/j.peptides.2020.170328.WHO Coronavirus (COVID-19) dashboard. 2023. https://covid19.who.int/?mapFilter=cases).WHO Coronavirus (COVID-19) dashboard. 2023. https://covid19.who.int/?mapFilter=cases).Галегов Г. А. Этиотропная лекарственная терапия вирусных инфекций. Вопросы вирусологии. 2004; 3: 35–40.Galegov G. A. Etiotropnaya lekarstvennaya terapiya virusnykh infektsij. Voprosy Virusologii. 2004; 3: 35–40. (in Russian)Бовин Н. В. Новые подходы к противовирусной терапии. Молекулярная медицина. 2004;. 3: 56–61.Bovin N. V. Novye podkhody k pro-tivovirusnoj terapii. Molekulyarnaya Meditsina. 2004;. 3: 56–61. (in Russian)Избранные материалы Российской заочной электронной научнопрактической конференции «Создание и клинические испытания лекарственных средств. Современная фармакотерапия вирусных инфекций» (7–12 ноября 2005 года, г. Волгоград). Лекарственный вестник. 2006; 3 (5): 37–54.Izbrannye materialy Rossijskoj zaochnoj elektronnoj nauchno-prakticheskoj konferentsii «Sozdanie i klinicheskie ispytaniya lekarstvennykh sredstv. Sovremennaya farmakoterapiya virusnykh infektsij» (7–12 noyabrya 2005 goda, g. Volgograd). Lekarstvennyj vestnik. 2006; 3 (5): 37–54. (in Russian)]Goncalves B. C., Barbosa M. G. L., Olak A. P. S. et al. Antiviral therapies: Advances and perspectives. Fundam Clin Pharmacol. 2021; 35: 305–320. doi: 10.1111/fcp.12609.Goncalves B. C., Barbosa M. G. L., Olak A. P. S. et al. Antiviral therapies: Advances and perspectives. Fundam Clin Pharmacol. 2021; 35: 305–320. doi: 10.1111/fcp.12609.De Clercq E., Li G. Approved antiviral drugs over the past 50 years. Clin Microbiol Rev. 2016; 29: 695–747. doi: 10.1128/CMR.00102-15.De Clercq E., Li G. Approved antiviral drugs over the past 50 years. Clin Microbiol Rev. 2016; 29: 695–747. doi: 10.1128/CMR.00102-15.Hughes D., Andersson D. I. Evolutionary consequences of drug resistance: Shared principles across diverse targets and organisms. Nat Rev Genet. 2015; 16: 459–471. doi: 10.1038/nrg3922.Hughes D., Andersson D. I. Evolutionary consequences of drug resistance: Shared principles across diverse targets and organisms. Nat Rev Genet. 2015; 16: 459–471. doi: 10.1038/nrg3922.Cele S., Jackson L., Khoury V. et al. Omicron extensively but incompletely escapes Pfizer B. N.T162b2 neutralization. Nature. 2022; 602: 654–656. doi: 10.1038/s41586-021-04387-1.Cele S., Jackson L., Khoury V. et al. Omicron extensively but incompletely escapes Pfizer B. N.T162b2 neutralization. Nature. 2022; 602: 654–656. doi: 10.1038/s41586-021-04387-1.Outlaw V. K., Bovier F. T., Mears M. C. et al. Inhibition of Coronavirus Entry in vitro and ex vivo by a lipid-conjugated peptide derived from the SARS-CoV-2 spike glycoprotein HRC domain. mBio. 2020; 11: e01935–20. doi: 10.1128/mBio.01935-20.Outlaw V. K., Bovier F. T., Mears M. C. et al. Inhibition of Coronavirus Entry in vitro and ex vivo by a lipid-conjugated peptide derived from the SARS-CoV-2 spike glycoprotein HRC domain. mBio. 2020; 11: e01935–20. doi: 10.1128/mBio.01935-20.de Vries R. D., Schmitz K. S., Bovier F. T. et al. Intranasal fusion inhibitory lipopeptide prevents direct-contact SARS-CoV-2 transmission in ferrets. Science. 2021; 371: 1379–1382. doi: 10.1126/science.abf4896.de Vries R. D., Schmitz K. S., Bovier F. T. et al. Intranasal fusion inhibitory lipopeptide prevents direct-contact SARS-CoV-2 transmission in ferrets. Science. 2021; 371: 1379–1382. doi: 10.1126/science.abf4896.Luteijn R. D., Praest P., Thiele F. et al. A broad-spectrum antiviral peptide blocks infection of viruses by binding to phosphatidylserine in the viral envelope. Cells. 2020; 9: 1989. doi: 10.3390/cells9091989.Luteijn R. D., Praest P., Thiele F. et al. A broad-spectrum antiviral peptide blocks infection of viruses by binding to phosphatidylserine in the viral envelope. Cells. 2020; 9: 1989. doi: 10.3390/cells9091989.Brice D. C., Diamond G. Antiviral Activities of Human Host Defense Peptides. Curr Med Chem. 2020; 27: 1420–1443. doi: 10.2174/0929867326666190805151654.Brice D. C., Diamond G. Antiviral Activities of Human Host Defense Peptides. Curr Med Chem. 2020; 27: 1420–1443. doi: 10.2174/0929867326666190805151654.Kim M. I., Pham T. K., Kim D. et al. Identification of brevinin-1EMaderived stapled peptides as broad-spectrum virus entry blockers. Virology. 2021; 561: 6–16. doi: 10.1016/j.virol.2021.05.004.Kim M. I., Pham T. K., Kim D. et al. Identification of brevinin-1EMaderived stapled peptides as broad-spectrum virus entry blockers. Virology. 2021; 561: 6–16. doi: 10.1016/j.virol.2021.05.004.Zhao H., Zhou J., Zhang K. et al. A novel peptide with potent and broadspectrum antiviral activities against multiple respiratory viruses. Sci Rep. 2016; 6: 22008. doi: 10.1038/srep22008.Zhao H., Zhou J., Zhang K. et al. A novel peptide with potent and broadspectrum antiviral activities against multiple respiratory viruses. Sci Rep. 2016; 6: 22008. doi: 10.1038/srep22008.Sample C. J., Hudak K. E., Barefoot B. E. et al. A mastoparan-derived peptide has broad-spectrum antiviral activity against enveloped viruses. Peptides. 2013; 48: 96–105. doi: 10.1016/j.peptides.2013.07.014.Sample C. J., Hudak K. E., Barefoot B. E. et al. A mastoparan-derived peptide has broad-spectrum antiviral activity against enveloped viruses. Peptides. 2013; 48: 96–105. doi: 10.1016/j.peptides.2013.07.014.Li Q., Zhao Z., Zhou D. et al. Virucidal activity of a scorpion venom peptide variant mucroporin-M1 against measles, SARS-CoV and influenza H5N1 viruses. Peptides. 2011; 32: 1518–1525. doi: 10.1016/j.peptides.2011.05.015.Li Q., Zhao Z., Zhou D. et al. Virucidal activity of a scorpion venom peptide variant mucroporin-M1 against measles, SARS-CoV and influenza H5N1 viruses. Peptides. 2011; 32: 1518–1525. doi: 10.1016/j.peptides.2011.05.015.Lu S., Pan X., Chen D. et al. Broad-spectrum antivirals of protoporphyrins inhibit the entry of highly pathogenic emerging viruses. Bioorg Chem. 2021; 107: 104619. doi: 10.1016/j.bioorg.2020.104619.Lu S., Pan X., Chen D. et al. Broad-spectrum antivirals of protoporphyrins inhibit the entry of highly pathogenic emerging viruses. Bioorg Chem. 2021; 107: 104619. doi: 10.1016/j.bioorg.2020.104619.ElSawy K.M., Twarock R., Verma C. S., Caves L. S. Peptide inhibitors of viral assembly: A novel route to broad-spectrum antivirals. J Chem Inf Model. 2012; 52: 770–776. doi: 10.1021/ci200467s.ElSawy K.M., Twarock R., Verma C. S., Caves L. S. Peptide inhibitors of viral assembly: A novel route to broad-spectrum antivirals. J Chem Inf Model. 2012; 52: 770–776. doi: 10.1021/ci200467s.Zannella C., Mosca F., Mariani F. et al. Microbial Diseases of Bivalve Mollusks: Infections, Immunology and Antimicrobial Defense. Mar Drugs. 2017; 15: 182. doi: 10.3390/md15060182.Zannella C., Mosca F., Mariani F. et al. Microbial Diseases of Bivalve Mollusks: Infections, Immunology and Antimicrobial Defense. Mar Drugs. 2017; 15: 182. doi: 10.3390/md15060182.Pessi A., Bixler S. L., Soloveva V. et al. Cholesterol-conjugated stapled peptides inhibit Ebola and Marburg viruses in vitro and in vivo. Antivir Res. 2019; 171: 104592. doi: 10.1016/j.antiviral.2019.104592.Pessi A., Bixler S. L., Soloveva V. et al. Cholesterol-conjugated stapled peptides inhibit Ebola and Marburg viruses in vitro and in vivo. Antivir Res. 2019; 171: 104592. doi: 10.1016/j.antiviral.2019.104592.Benedict A., Bansal N., Senina S. et al. Repurposing F. D.A-approved drugs as therapeutics to treat Rift Valley fever virus infection. Front Microbiol. 2015; 6: 676. doi: 10.3389/fmicb.2015.00676.Benedict A., Bansal N., Senina S. et al. Repurposing F. D.A-approved drugs as therapeutics to treat Rift Valley fever virus infection. Front Microbiol. 2015; 6: 676. doi: 10.3389/fmicb.2015.00676.Descamps V., Helle F., CLouandre C. et al. The kinase-inhibitor sorafenib inhibits multiple steps of the Hepatitis C Virus infectious cycle in vitro. Antiviral Res. 2015; 118: 93–102. doi: 10.1016/j.antiviral.2015.03.012.Descamps V., Helle F., CLouandre C. et al. The kinase-inhibitor sorafenib inhibits multiple steps of the Hepatitis C Virus infectious cycle in vitro. Antiviral Res. 2015; 118: 93–102. doi: 10.1016/j.antiviral.2015.03.012.Gao M., Duan H., Liu J. et al. The multi-targeted kinase inhibitor sorafenib inhibits enterovirus 71 replication by regulating IRES-dependent translation of viral proteins. Antiviral Res. 2014; 106: 80–5. doi: 10.1016/j.antiviral.2014.03.009.Gao M., Duan H., Liu J. et al. The multi-targeted kinase inhibitor sorafenib inhibits enterovirus 71 replication by regulating IRES-dependent translation of viral proteins. Antiviral Res. 2014; 106: 80–5. doi: 10.1016/j.antiviral.2014.03.009.Michaelis M., Paulus C., N. Loschmann N. et al. The multi-targeted kinase inhibitor sorafenib inhibits human cytomegalovirus replication. Cell Mol Life Sci. 2011; 68 (6): 1079–90. doi: 10.1007/s00018-010-0510-8.Michaelis M., Paulus C., N. Loschmann N. et al. The multi-targeted kinase inhibitor sorafenib inhibits human cytomegalovirus replication. Cell Mol Life Sci. 2011; 68 (6): 1079–90. doi: 10.1007/s00018-010-0510-8.Randhawa P. S., Farasati N. A., Y. Huang Y. et al. Viral drug sensitivity testing using quantitative PCR: effect of tyrosine kinase inhibitors on polyomavirus BK replication. Am J Clin Pathol. 2010; 134 (6): 916–20. doi: 10.1309/AJCP7JYHJN1PGQVC.Randhawa P. S., Farasati N. A., Y. Huang Y. et al. Viral drug sensitivity testing using quantitative PCR: effect of tyrosine kinase inhibitors on polyomavirus BK replication. Am J Clin Pathol. 2010; 134 (6): 916–20. doi: 10.1309/AJCP7JYHJN1PGQVC.Roberts J. L., Tavallai M., A. Nourbakhsh A. et al. GRP78/Dna K Is a target for nexavar/stivarga/votrient in the treatment of human malignancies, viral infections and bacterial diseases. J Cell Physiol. 2015; 230 (10): 2552–78. doi: 10.1002/jcp.25014.Roberts J. L., Tavallai M., A. Nourbakhsh A. et al. GRP78/Dna K Is a target for nexavar/stivarga/votrient in the treatment of human malignancies, viral infections and bacterial diseases. J Cell Physiol. 2015; 230 (10): 2552–78. doi: 10.1002/jcp.25014.Brahms A., Mudhasani R., Pinkham C. et al. Sorafenib impedes rift valley fever virus egress by inhibiting valosin-containing protein function in the cellular secretory pathway. J Virol. 2017; 91 (21): e00968–17. doi: 10.1128/jvi.00968-17.Brahms A., Mudhasani R., Pinkham C. et al. Sorafenib impedes rift valley fever virus egress by inhibiting valosin-containing protein function in the cellular secretory pathway. J Virol. 2017; 91 (21): e00968–17. doi: 10.1128/jvi.00968-17.De Angelis M., Casciaro B., Genovese A. et al. Temporin G., an amphibian antimicrobial peptide against influenza and parainfluenza respiratory viruses: insights into biological activity and mechanism of action. FASEB J. 2021; 35: e21358. doi: 10.1096/fj.202001885RR.De Angelis M., Casciaro B., Genovese A. et al. Temporin G., an amphibian antimicrobial peptide against influenza and parainfluenza respiratory viruses: insights into biological activity and mechanism of action. FASEB J. 2021; 35: e21358. doi: 10.1096/fj.202001885RR.Логинова С. Я., Борисевич С. В., Максимов В. А., Бондарев В. П., Котовская С. К., Русинов В. Л., Чарушин В. Н., Чупахин О. Н. Лечебная эффективность нового отечественного химиопрепарата Триазавирин в отношении возбудителя гриппа А (H5N1). Антибиотики и химиотер. 2011; 56 (1–2): 10–12.Loginova S. A., Borisevich S. V., Maksimov V. A., Bondarev V. P., Kotovskaya S. K., Rusinov V. L., Charushkin V. N., Chupakhin O. N. Therapeutic efficacy of triazavirin, a novel russian chemotherapeutic, against influenza virus A (H5N1). Antibiot Khimioter = Antibiotics and Chemotherapy. 2011; 56 (1-2): 10–12. (in Russian)]Логинова С. Я., Борисевич С. В., Русинов В. Л., Уломский Е. Н., Чарушин В. Н., Чупахин О. Н., Сорокин П. В. Изучение лечебной эффективности Триазавирина в отношении экспериментальной формы клещевого энцефалита у белых мышей. Антибиотики и химиотер. 2015; 60 (7–8): 11–13.Loginova S.Ya., Borisevich S. V., Rusinov V. L., Ulomsky E. N., Charushin V. N., Chupakhin O. N., Sorokin P. V. Investigation of therapeutic efficacy of triazavirin against experimental forest-spring encephalitis on albino mice. Antibiot Khimioter = Antibiotics and Chemotherapy. 2015; 60 (7-8): 11–13. (in Russian)Логинова С. Я., Борисевич С. В., Русинов В. Л., Уломский У. Н., Чарушин В. Н., Чупахин О. Н., Сорокин П. В. Изучение профилактической эффективности Триазавирина в отношении экспериментальной формы клещевого энцефалита у белых мышей. Антибиотики и химиотер. 2015; 60 (5–6): 8–11.Loginova S. Ya., Borisevich S. V., Rusinov V. L., Ulomsky U. N., Charushin V. N., Chupakhin O. N., Sorokin P. V. Investigation of prophylactic efficacy of triazavirin against experimental forest-spring encephalitis on albino mice. Antibiot Khimioter = Antibiotics and Chemotherapy. 2015; 60 (5-6): 8. (in Russian)Kok W. M. New developments in flavivirus drug discovery. Expert Opin Drug Discov. 2016; 11 (5): 433–45. doi: 10.1517/17460441.2016.1160887.Kok W. M. New developments in flavivirus drug discovery. Expert Opin Drug Discov. 2016; 11 (5): 433–45. doi: 10.1517/17460441.2016.1160887.De Clercq E. Antiviral agents: characteristic activity spectrum depending on the molecular target with which they interact. Adv Virus Res. 1993; 42: 1–55. doi: 10.1016/s0065-3527(08)60082-2.De Clercq E. Antiviral agents: characteristic activity spectrum depending on the molecular target with which they interact. Adv Virus Res. 1993; 42: 1–55. doi: 10.1016/s0065-3527(08)60082-2.Логинова С. Я., Борисевич С. В., Максимов В. А., Бондарев В. П., Небольсин В. Е. Изучение лечебной эффективности нового отечественного химиопрепарата Ингавирин® в отношении возбудителя гриппа А (H3N2). Антибиотики и химиотер. 2008; 53 (7–8): 27–30.Loginova S. Ya., Borisevich S. V., Maksimov V. A., Bondarev V. P., Nebolsin V. E.Therapeutic efficacy of Ingavirin®, a new russian formulation against influenza a virus (H3N2). Antibiot Khimioter = Antibiotics and Chemotherapy. 2008; 53 (7–8): 27–30. (in Russian)Логинова С. Я., Борисевич С. В., Лыков М. В., Веденина Е. В., Борисевич Г. В., Бондарев В. П., Небольсин В. Е., Чучалин А. Г. Изучение эффективности Ингавирина® in vitro в отношении «мексиканского» пандемического подтипа H1N1 вируса гриппа А, штаммы A/California/04/2009 и A/California/07/2009 Антибиотики и химиотер. 2009; 54 (3–4): 15–17.Loginova S.Ya., Borisevich S. V., Lykov M. V., Vedenina E. V., Borisevich G. V., Bondarev V. P., Nebolsin V. E., Chuchalin A. G. In vitro efficacy of ingavirin against the mexican pandemic subtype H1N1 of influenza A virus, strains A/California/04/2009 and A/California/07/2009. Antibiot Khimioter = Antibiotics and Chemotherapy. 2009; 54 (3–4): 15–17. (in Russian)Poordad F., McCone J., Bacon B. R. et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011; 364 (13): 1195–1206.Poordad F., McCone J., Bacon B. R. et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011; 364 (13): 1195–1206.De Clercq E. Highlights in antiviral drug research: antivirals at the horizon. Med Res Rev. 2013; 33 (6): 1215–1248. doi: 10.1002/med.2125De Clercq E. Highlights in antiviral drug research: antivirals at the horizon. Med Res Rev. 2013; 33 (6): 1215–1248. doi: 10.1002/med.2125Wu S. F., Lee C.-J., Liao C.-L. et al. Antiviral effects of an iminosugar derivative on flavivirus infections. J Virol. 2002; 76 (8): 3596–3604. doi: 10.1128/jvi.76.8.3596-3604.2002.Wu S. F., Lee C.-J., Liao C.-L. et al. Antiviral effects of an iminosugar derivative on flavivirus infections. J Virol. 2002; 76 (8): 3596–3604. doi: 10.1128/jvi.76.8.3596-3604.2002.McCormick J. B., King L. J., Webb P. A. et al. Lassa fever. Effective therapy with ribavirin. N Engl J Med. 1986; 314 (1): 20–26. doi: 10.1056/NEJM198601023140104.McCormick J. B., King L. J., Webb P. A. et al. Lassa fever. Effective therapy with ribavirin. N Engl J Med. 1986; 314 (1): 20–26. doi: 10.1056/NEJM198601023140104.Хаггинс Д., Сян ЧюБ Кросгрифф Т. и др. Перспективное, дважды шифрованное, одновременное, плацебо-контролируемое клиническое иследование внутривенной терапии рибавирином геморрагической лихорадки с почечным синдромом (ГЛПС). Международный симппозиум по ГЛПС, 5–10 мая, 1991, Ленинград. 1991; 15.Khaggins D., Syan ChyuB Krosgriff T. i dr. Perspektivnoe, dvazhdy shifrovannoe, odnovremennoe, platsebo-kontroliruemoe klinicheskoe isledovanie vnutrivennoj terapii ribavirinom gemorragicheskoj likhoradki s pochechnym sindromom (GLPS). Mezhdunarodnyj simppozium po GLPS, 5–10 maya, 1991, Leningrad. 1991; 15. (in Russian)Huggins J. W., Hsiang C. M., Cosgriff T. M. Chemotherapy of HFRS. 1-st Int. Conf. HFRS, may 4–6, 1989, Seoul, Korea — Seoul, 1989; 84.Huggins J. W., Hsiang C. M., Cosgriff T. M. Chemotherapy of HFRS. 1-st Int. Conf. HFRS, may 4–6, 1989, Seoul, Korea — Seoul, 1989; 84.Watts D. M., Ussery M. A., Nash D., Peters C. J. Inhibition of CrimeanCongo hemorrahagic fever viral infectivity yields in vitro by ribavirin. Am J Trop Med Hyg. 1989; 41 (5): 581–585. doi: 10.4269/ajtmh.1989.41.581.Watts D. M., Ussery M. A., Nash D., Peters C. J. Inhibition of CrimeanCongo hemorrahagic fever viral infectivity yields in vitro by ribavirin. Am J Trop Med Hyg. 1989; 41 (5): 581–585. doi: 10.4269/ajtmh.1989.41.581.Sterhen E. L., Jones D. E., Peters C. J. et al. Ribavirn treatment of toga-, arena- and bunyaviruses infection in subhuman primates and other animal species. In: Ribavirin broad spectrum agent. R. A. Smith (ed.). Acad. Press, 1980; 4: 170–174.Sterhen E. L., Jones D. E., Peters C. J. et al. Ribavirn treatment of toga-, arena- and bunyaviruses infection in subhuman primates and other animal species. In: Ribavirin broad spectrum agent. R. A. Smith (ed.). Acad. Press, 1980; 4: 170–174.Delang L., Guerrero N. S., Tas A. et al. Mutations in the chikungunya virus non-structural proteins cause resistance to favipiravir (T-705), a broadspectrum antiviral. J Antimicrob Chemother. 2014; 69 (10): 2770–2784. doi: 10.1093/jac/dku209.Delang L., Guerrero N. S., Tas A. et al. Mutations in the chikungunya virus non-structural proteins cause resistance to favipiravir (T-705), a broadspectrum antiviral. J Antimicrob Chemother. 2014; 69 (10): 2770–2784. doi: 10.1093/jac/dku209.Bassetto M., de Burghgraeve T., Delang L. et al. Computer-aided identification, design and synthesis of a novel series of compounds with selective antiviral activity against chikungunya virus. Antiviral Res. 2013; 98 (1): 12–18. doi: 10.1016/j.antiviral.2013.01.002.Bassetto M., de Burghgraeve T., Delang L. et al. Computer-aided identification, design and synthesis of a novel series of compounds with selective antiviral activity against chikungunya virus. Antiviral Res. 2013; 98 (1): 12–18. doi: 10.1016/j.antiviral.2013.01.002.Parashar D., Cherian S. Antiviral perspectives for chikungunya virus. Biomed Res Int. 2014; 631642. doi: 10.1155/2014/631642.Parashar D., Cherian S. Antiviral perspectives for chikungunya virus. Biomed Res Int. 2014; 631642. doi: 10.1155/2014/631642.Kim J. A., Seong R. K., Kumar M., Shin O. S. Favipiravir and ribavirin inhibit replication of Asian and African strains of Zika Virus in different cell models. Viruses. 2018; 10 (2): E72. doi: 10.3390/v10020072.Kim J. A., Seong R. K., Kumar M., Shin O. S. Favipiravir and ribavirin inhibit replication of Asian and African strains of Zika Virus in different cell models. Viruses. 2018; 10 (2): E72. doi: 10.3390/v10020072.Cai L., Sun Y., Song Y. et al. Viral polymerase inhibitors T-705 and T-1105 are potential inhibitors of Zika virus replication. Arch Virol. 2017; 162 (9): 2847–2853. doi: 10.1007/s00705-017-3436-8.Cai L., Sun Y., Song Y. et al. Viral polymerase inhibitors T-705 and T-1105 are potential inhibitors of Zika virus replication. Arch Virol. 2017; 162 (9): 2847–2853. doi: 10.1007/s00705-017-3436-8.Julander J. G., Shafer K., Smee D. F. et al. Activity of T-705 in a hamster model of yellow fever virus infection in comparison with that of a chemically related compound, T-1106. Antimicrob Agents Chemother. 2009; 53 (1): 202–209. doi: 10.1128/AAC.01074-08.Julander J. G., Shafer K., Smee D. F. et al. Activity of T-705 in a hamster model of yellow fever virus infection in comparison with that of a chemically related compound, T-1106. Antimicrob Agents Chemother. 2009; 53 (1): 202–209. doi: 10.1128/AAC.01074-08.Morrey J. D., Smee D. F., Sidwell R. W., Tseng C. K. Identification of active compounds against a New York isolate of West Nile virus. Antiviral Research. 2002; 55: 107–116. doi: 10.1016/s0166-3542(02)00013-x.Morrey J. D., Smee D. F., Sidwell R. W., Tseng C. K. Identification of active compounds against a New York isolate of West Nile virus. Antiviral Research. 2002; 55: 107–116. doi: 10.1016/s0166-3542(02)00013-x.Gowen B. B., Wong M. H., Jung K. H. et al. In vitro and in vivo activities of T-705 against arenavirus and bunyavirus infections. Antimicrob. Agents Chemother. 2007; 51: 3168–3176. doi: 10.1128/AAC.00356-07.Gowen B. B., Wong M. H., Jung K. H. et al. In vitro and in vivo activities of T-705 against arenavirus and bunyavirus infections. Antimicrob. Agents Chemother. 2007; 51: 3168–3176. doi: 10.1128/AAC.00356-07.Oestereich L., Rieger T., Lüdtke A. et al. Efficacy of favipiravir alone and in combination with ribavirin in a lethal, immunocompetent mouse model of Lassa fever. J Infect Dis. 2016; 213: 934–938. doi: 10.1093/infdis/jiv522.Oestereich L., Rieger T., Lüdtke A. et al. Efficacy of favipiravir alone and in combination with ribavirin in a lethal, immunocompetent mouse model of Lassa fever. J Infect Dis. 2016; 213: 934–938. doi: 10.1093/infdis/jiv522.Westover J. B., Sefing E. J., Bailey K. W. et al. Low-dose ribavirin potentiates the antiviral activity of favipiravir against hemorrhagic fever viruses. Antiviral Res. 2016; 126: 62–68. doi: 10.1016/j.antiviral.2015.12.006.Westover J. B., Sefing E. J., Bailey K. W. et al. Low-dose ribavirin potentiates the antiviral activity of favipiravir against hemorrhagic fever viruses. Antiviral Res. 2016; 126: 62–68. doi: 10.1016/j.antiviral.2015.12.006.Rosenke K., Feldmann H., Westover J. B. et al. Use of favipiravir to treat lassa virus infection in macaques. Emerg Infect Dis. 2018; 24 (9): 1696–1699. doi: 10.3201/eid2409.180233.Rosenke K., Feldmann H., Westover J. B. et al. Use of favipiravir to treat lassa virus infection in macaques. Emerg Infect Dis. 2018; 24 (9): 1696–1699. doi: 10.3201/eid2409.180233.Oestereich L., Ludtke A., Wurr S. et al. Successful treatment of advanced Ebola virus infection with T-705 (favipiravir) in a small animal model. Antiviral Res. 2014; 105: 17–21. doi: 10.1016/j.antiviral.2014.02.014.Oestereich L., Ludtke A., Wurr S. et al. Successful treatment of advanced Ebola virus infection with T-705 (favipiravir) in a small animal model. Antiviral Res. 2014; 105: 17–21. doi: 10.1016/j.antiviral.2014.02.014.Smither S. J., Eastaugh L. S., Steward J. A. et al. Post-exposure efficacy of oral T-705 (Favipiravir) against inhalational Ebola virus infection in a mouse model. Antiviral Res. 2014; 104: 153–155. doi: 10.1016/j.antiviral.2014.01.012.Smither S. J., Eastaugh L. S., Steward J. A. et al. Post-exposure efficacy of oral T-705 (Favipiravir) against inhalational Ebola virus infection in a mouse model. Antiviral Res. 2014; 104: 153–155. doi: 10.1016/j.antiviral.2014.01.012.Bai C. Q., Mu J.S., Kargbo D., Song Y. B. et al. Clinical and virological characteristics of ebola virus disease patients treated with favipiravir (T-705)- Sierra Leone, 2014. Clin Infect Dis. 2016; 63 (10): 1288–1294. doi: 10.1093/cid/ciw571.Bai C. Q., Mu J.S., Kargbo D., Song Y. B. et al. Clinical and virological characteristics of ebola virus disease patients treated with favipiravir (T-705)- Sierra Leone, 2014. Clin Infect Dis. 2016; 63 (10): 1288–1294. doi: 10.1093/cid/ciw571.Sissoko D., Laouenan C., Folkesson E. et al. Experimental treatment with favipiravir for ebola virus disease (the JIKI trial): a historically controlled, single-arm proof-of-concept trial in Guinea. PLoS Med. 2016; 13 (3): e1001967. doi: 10.1371/journal.pmed.1001967.Sissoko D., Laouenan C., Folkesson E. et al. Experimental treatment with favipiravir for ebola virus disease (the JIKI trial): a historically controlled, single-arm proof-of-concept trial in Guinea. PLoS Med. 2016; 13 (3): e1001967. doi: 10.1371/journal.pmed.1001967.Schibler M., Vetter P., Cherpillod P. et al. Clinical features and viral kinetics in a rapidly cured patient with Ebola virus disease: a case report. Lancet Infect Dis. 2015; 15 (9): 1034–1040. doi: 10.1016/S1473-3099(15)00229-7.Schibler M., Vetter P., Cherpillod P. et al. Clinical features and viral kinetics in a rapidly cured patient with Ebola virus disease: a case report. Lancet Infect Dis. 2015; 15 (9): 1034–1040. doi: 10.1016/S1473-3099(15)00229-7.Mora-Rillo M., Arsuaga M., Ramirez-Olivencia G. et al. Acute respiratory distress syndrome after convalescent plasma use: treatment of a patient with Ebola virus disease contracted in Madrid, Spain. Lancet Respir Med. 2015; 3 (7): 554–562. doi: 10.1016/S2213-2600 (15)00180-0.Mora-Rillo M., Arsuaga M., Ramirez-Olivencia G. et al. Acute respiratory distress syndrome after convalescent plasma use: treatment of a patient with Ebola virus disease contracted in Madrid, Spain. Lancet Respir Med. 2015; 3 (7): 554–562. doi: 10.1016/S2213-2600 (15)00180-0.Zhu W., Zhang Z., He S. et al. Successful treatment of Marburg virus with orally administrated T-705 (Favipiravir) in a mouse model. Antiviral Res. 2018 Mar; 151: 39–49. doi: 10.1016/j.antiviral.2018.01.011.Zhu W., Zhang Z., He S. et al. Successful treatment of Marburg virus with orally administrated T-705 (Favipiravir) in a mouse model. Antiviral Res. 2018 Mar; 151: 39–49. doi: 10.1016/j.antiviral.2018.01.011.Dawes B. E., Kalveram B., Ikegami T. et al. Favipiravir (T-705) protects against Nipah virus infection in the hamster model. Sci Rep. 2018; 8 (1): 7604. doi: 10.1038/s41598-018-25780-3.Dawes B. E., Kalveram B., Ikegami T. et al. Favipiravir (T-705) protects against Nipah virus infection in the hamster model. Sci Rep. 2018; 8 (1): 7604. doi: 10.1038/s41598-018-25780-3.Morrey J. D., Taro B. S., Siddharthan V. et al. Efficacy of orally administered T-705 pyrazine analog on lethal West Nile virus infection in rodents. Antiviral Res. 2008; 80 (3): 377–379. doi: 10.1016/j.antiviral.2008.07.009.Morrey J. D., Taro B. S., Siddharthan V. et al. Efficacy of orally administered T-705 pyrazine analog on lethal West Nile virus infection in rodents. Antiviral Res. 2008; 80 (3): 377–379. doi: 10.1016/j.antiviral.2008.07.009.Qiu L., Patterson S. E., Bonnac L. F., Geraghty R. J. Nucleobases and corresponding nucleosides display potent antiviral activities against dengue virus possibly through viral lethal mutagenesis. PLoS Negl Trop Dis. 2018; 12 4): e0006421. doi: 10.1371/journal.pntd.0006421.Qiu L., Patterson S. E., Bonnac L. F., Geraghty R. J. Nucleobases and corresponding nucleosides display potent antiviral activities against dengue virus possibly through viral lethal mutagenesis. PLoS Negl Trop Dis. 2018; 12 4): e0006421. doi: 10.1371/journal.pntd.0006421.Caroline A. L., Powell D. S., Bethel L. M. et al. Broad spectrum antiviral activity of favipiravir (T-705): protection from highly lethal inhalational Rift Valley Fever. PLoS Negl Trop Dis. 2014; 8 (4): 2790. doi: 10.1371/journal.pntd.0002790.Caroline A. L., Powell D. S., Bethel L. M. et al. Broad spectrum antiviral activity of favipiravir (T-705): protection from highly lethal inhalational Rift Valley Fever. PLoS Negl Trop Dis. 2014; 8 (4): 2790. doi: 10.1371/journal.pntd.0002790.Julander J. G., Smee D. F., Morrey J. D., Furuta Y. Effect of T-705 treatment on western equine encephalitis in a mouse model. Antiviral Res. 2009; 82 (3): 169–171. doi: 10.1016/j.antiviral.2009.02.201.Julander J. G., Smee D. F., Morrey J. D., Furuta Y. Effect of T-705 treatment on western equine encephalitis in a mouse model. Antiviral Res. 2009; 82 (3): 169–171. doi: 10.1016/j.antiviral.2009.02.201.Marathe B. M., Wong S.-S., Vogel P. et al. Combinations of oseltamivir and t-705 extend the treatment window for highly pathogenic influenza A (H5N1) virus infection in mice. Sci Rep. 2016; 6: 26742. doi: 10.1038/srep26742.Marathe B. M., Wong S.-S., Vogel P. et al. Combinations of oseltamivir and t-705 extend the treatment window for highly pathogenic influenza A (H5N1) virus infection in mice. Sci Rep. 2016; 6: 26742. doi: 10.1038/srep26742.Boyd J. E., Sommerville R. G. The antiviral activity of some related benzo (b)thiophene derivatives. II. Antiinfluenza activity. Arch Ges Virusforsch. 1974; 46 (1–2): 78–85. doi: 10.1007/BF01240207.Boyd J. E., Sommerville R. G. The antiviral activity of some related benzo (b)thiophene derivatives. II. Antiinfluenza activity. Arch Ges Virusforsch. 1974; 46 (1–2): 78–85. doi: 10.1007/BF01240207.Sobolevsky A. I., Koshelev S. G., Khodorov B. I. Molecular size and hydrophobicity as factors which determine the efficacy of the blocking action of amino-adamantane derivatives on NMDA channels. Membr Cell Biol. 1999; 13 (1): 79–93.Sobolevsky A. I., Koshelev S. G., Khodorov B. I. Molecular size and hydrophobicity as factors which determine the efficacy of the blocking action of amino-adamantane derivatives on NMDA channels. Membr Cell Biol. 1999; 13 (1): 79–93.Griffin S. D., Harvey R., Clarke D. S. et al. A conserved basic loop in hepatitis C virus p7 protein is required for amantadine-sensitive ion channel activity in mammalian cells but is dispensable for localization to mitochondria. J Gen Virol. 2004; 85 (Pt 2): 451–461. doi: 10.1099/vir.0.19634-0.Griffin S. D., Harvey R., Clarke D. S. et al. A conserved basic loop in hepatitis C virus p7 protein is required for amantadine-sensitive ion channel activity in mammalian cells but is dispensable for localization to mitochondria. J Gen Virol. 2004; 85 (Pt 2): 451–461. doi: 10.1099/vir.0.19634-0.Griffin S. D.C., Beales L. P., Clarcke D. S. et al. The p7 protein of hepatitis C virus forms an ion channel that is blocked by the antiviral drug, amantadine. FEBS Lett. 2003; 535: 34–38. doi: 10.1016/s0014-5793(02)03851-6.Griffin S. D.C., Beales L. P., Clarcke D. S. et al. The p7 protein of hepatitis C virus forms an ion channel that is blocked by the antiviral drug, amantadine. FEBS Lett. 2003; 535: 34–38. doi: 10.1016/s0014-5793(02)03851-6.Kelly M. L., Cook J. A., Brown-Augsburger P. et al. Demonstrating the intrinsic ion channel activity of virally encoded proteins. FEBS Lett. 2003; 552: 61–67. doi: 10.1016/s0014-5793(03)00851-2.Kelly M. L., Cook J. A., Brown-Augsburger P. et al. Demonstrating the intrinsic ion channel activity of virally encoded proteins. FEBS Lett. 2003; 552: 61–67. doi: 10.1016/s0014-5793(03)00851-2.Tanner J. A., Zheng B. J., Zhou J. et al. The Adamantane-derived bananins are potent inhibitors of the helicase activities and replication of SARS coronavirus. Chem Biol. 2005; 12 (3): 303–311. doi: 10.1016/j.chembiol.2005.01.006.Tanner J. A., Zheng B. J., Zhou J. et al. The Adamantane-derived bananins are potent inhibitors of the helicase activities and replication of SARS coronavirus. Chem Biol. 2005; 12 (3): 303–311. doi: 10.1016/j.chembiol.2005.01.006.Тимофеев Д. И., Перминова Н. Г., Сербин А. В. и др. ВИЧ-ингибирующая активность полианионных матриц и соединений на их оcнове, содержащих адамантановые и норборненовые фармакофоры. Антибиотики и химиотер. 2003; 48 (5): 33–41.Timofeyev D. I., Perminova N. G., Kiseleva Ya. Yu., Nekludov V. V., Vatolin G. Yu., Grebinik T. S., Timofeyev I. V., Serbin A. V., Kasyan L. I. HIV-inhibiting activity of polyanionic matrixes and based on them substances containing adamantane and norbornene pharmacophores. Antibiot Khimioter = Antibiotics and Chemotherapy. 2003; 48 (5): 33–41. (in Russian)Сербин А. В., Алиханова О. Л., Тимофеев И. В. и др. Роль мембранотропных алициклических фармакофоров в терапевтической защите от вируса иммунодефицита человека (ВИЧ). Перспективы развития химии и практического применения алициклических соединений. Тезисы докладов международной научно-технической конференциию Самара, 2004; 37–38.Serbin A. V., Alikhanova O. L., Timofeev I. V. i dr. Rol' membranotropnykh alitsiklicheskikh farmakoforov v terapevticheskoj zashchite ot virusa immunodefitsita cheloveka (VICh). Perspektivy razvitiya khimii i prakticheskogo primeneniya alitsiklicheskikh soedinenij. Tezisy dokladov mezhdunarodnoj nauchno-tekhnicheskoj konferentsiiyu Samara, 2004; 37–38. (in Russian)Burstein M. E., Serbin A.V., Khakhulina T. V. et al. Inhibition of HIV-1 replication by newly developed adamantane-containing polyanionic agents. Antiviral Res. 1999; 41 (3): 135–44.Burstein M. E., Serbin A.V., Khakhulina T. V. et al. Inhibition of HIV-1 replication by newly developed adamantane-containing polyanionic agents. Antiviral Res. 1999; 41 (3): 135–44.Сербин А. В., Климочкин Ю. Н., Стоцкая Л. Л. и др. Алициклические ингибиторы жизненного цикла вирусов. 1. Адамантансодержащие полианионные системы. Тезисы докладов международной научнотехнической конференции «Перспективы развития химии и практического применения алициклических соединений». Самара, 2004; 225.Serbin A. V., Klimochkin Yu. N., Stotskaya L. L. i dr. Alitsiklicheskie ingibitory zhiznennogo tsikla virusov. 1. Adamantansoderzhashchie polianionnye sistemy. Tezisy dokladov mezhdunarodnoj nauchno-tekhnicheskoj konferentsii «Perspektivy razvitiya khimii i prakticheskogo primeneniya alitsiklicheskikh soedinenij». Samara, 2004; 225. (in Russian)Козелецкая К. Л., Стоцкая Л. Л., Сербин А. В. и др. Структура и противовирусная активность адамантансодержащих полимерных препаратов. Вопросы вирусологии. 2003; 48 (5): 19–26.Kozeletskaya K. L., Stotskaya L. L., Serbin A. V. i dr. Struktura i protivovirusnaya aktivnost' adamantansoderzhashchikh polimernykh preparatov. Voprosy virusologii. 2003; 48 (5): 19–26. (in Russian)Rybalko S., Nesterova N., Diadiun S. et al. Therapeutical effect of modified adamantane copolymer compounds: study of molecular mechanisms. Acta Biochim Pol. 2001; 48 (1): 241–249.Rybalko S., Nesterova N., Diadiun S. et al. Therapeutical effect of modified adamantane copolymer compounds: study of molecular mechanisms. Acta Biochim Pol. 2001; 48 (1): 241–249.Horvat S., Varga-Defterdarovic L., Horvat J. et al. Synthesis and bioactivity studies of 1-adamantanamine derivatives of peptides. J Pept Sci. 1995; 1 (5): 303–310. doi: 10.1002/psc.310010505.Horvat S., Varga-Defterdarovic L., Horvat J. et al. Synthesis and bioactivity studies of 1-adamantanamine derivatives of peptides. J Pept Sci. 1995; 1 (5): 303–310. doi: 10.1002/psc.310010505.Vamecq J., Van derpoorten K., Poupaert J. H. et al. Anticonvulsant phenytoinergic pharmacophores and anti-HIV activity — preliminary evidence for the dual requirement of the 4-aminophthalimide platform and the N- (1-adamantyl) substitution for antiviral properties. Life Sci. 1998; 63 (19): 267–274. doi: 10.1016/s0024-3205(98)00445-7.Vamecq J., Van derpoorten K., Poupaert J. H. et al. Anticonvulsant phenytoinergic pharmacophores and anti-HIV activity — preliminary evidence for the dual requirement of the 4-aminophthalimide platform and the N- (1-adamantyl) substitution for antiviral properties. Life Sci. 1998; 63 (19): 267–274. doi: 10.1016/s0024-3205(98)00445-7.Barrientos L. G., O’Keefe B. R., Bray M. et al. Cyanovirin-N binds to the viral surface glycoprotein, GP1,2 and inhibits infectivity of Ebola virus. Antiviral Res. 2003; 58: 47–56. doi: 10.1016/s0166-3542(02)00183-3.Barrientos L. G., O’Keefe B. R., Bray M. et al. Cyanovirin-N binds to the viral surface glycoprotein, GP1,2 and inhibits infectivity of Ebola virus. Antiviral Res. 2003; 58: 47–56. doi: 10.1016/s0166-3542(02)00183-3.Щелкунов С. Н. Молекулярные факторы вирулентности ортопоксвирусов. Вестник РАМН. 1998; 3: 24–29.Shchelkunov S. N. Molekulyarnye faktory virulentnosti ortopoksvirusov. Vestnik RAMN. 1998; 3: 24–29. (in Russian)Matthew A. N., Leidner F., Lockbaum G. J. et al. Drug design strategies to avoid resistance in direct-acting antivirals and beyond. Chemical Reviews. 2021; 121: 3238–3270. doi: 10.1021/acs.chemrev.0c00648.Matthew A. N., Leidner F., Lockbaum G. J. et al. Drug design strategies to avoid resistance in direct-acting antivirals and beyond. Chemical Reviews. 2021; 121: 3238–3270. doi: 10.1021/acs.chemrev.0c00648.Adjei A. A. What is the right dose? The elusive optimal biologic dose in phase I clinical trials. J Clin Oncol. 2006; 24: 4054–4055. doi: 10.1200/JCO.2006.07.4658.Adjei A. A. What is the right dose? The elusive optimal biologic dose in phase I clinical trials. J Clin Oncol. 2006; 24: 4054–4055. doi: 10.1200/JCO.2006.07.4658.Fang Y., Wang J., Zhao M. et al. Progress and challenges in targeted protein degradation for neurodegenerative disease therapy. Journal of Medicinal Chemistry. 2022; 65: 11454–11477. doi: 10.1021/acs.jmedchem.2c00844.Fang Y., Wang J., Zhao M. et al. Progress and challenges in targeted protein degradation for neurodegenerative disease therapy. Journal of Medicinal Chemistry. 2022; 65: 11454–11477. doi: 10.1021/acs.jmedchem.2c00844.Liang G., Bushman F. D. The human virome: Assembly, composition and host interactions. Nat Rev Microbiol. 2021; 19: 514–527. doi: 10.1038/s41579-021-00536-5.Liang G., Bushman F. D. The human virome: Assembly, composition and host interactions. Nat Rev Microbiol. 2021; 19: 514–527. doi: 10.1038/s41579-021-00536-5.Illescas B. M., Rojo J., Delgado R., Martin N. Multivalent glycosylated nanostructures to inhibit Ebola virus infection. J Am Chem Soc. 2017; 139: 6018–6025. doi: 10.1021/jacs.7b01683.Illescas B. M., Rojo J., Delgado R., Martin N. Multivalent glycosylated nanostructures to inhibit Ebola virus infection. J Am Chem Soc. 2017; 139: 6018–6025. doi: 10.1021/jacs.7b01683.Schafer A., Xiong R., Cooper L. et al. Evidence for distinct mechanisms of small molecule inhibitors of filovirus entry. PLoS Pathog. 2021; 17 (2): e1009312. doi: 10.1371/journal.ppat.1009312.Schafer A., Xiong R., Cooper L. et al. Evidence for distinct mechanisms of small molecule inhibitors of filovirus entry. PLoS Pathog. 2021; 17 (2): e1009312. doi: 10.1371/journal.ppat.1009312.Kaptein S. J. F., Goethals O., Kiemel D. et al. A pan-serotype dengue virus inhibitor targeting the NS3–NS4B interaction. Nature. 2021; 598: 504– 509. doi: 10.1038/s41586-021-04123-9.Kaptein S. J. F., Goethals O., Kiemel D. et al. A pan-serotype dengue virus inhibitor targeting the NS3–NS4B interaction. Nature. 2021; 598: 504– 509. doi: 10.1038/s41586-021-04123-9.Pruijssers A. J., George A. S., Schafer A. et al. Remdesivir inhibits SARSCoV-2 in human lung cells and chimeric SARS-CoV expressing the SARSCoV-2 RNA polymerase in mice. Cell Reports. 2020; 32 (3): 107940. doi: 10.1016/j.celrep.2020.107940.Pruijssers A. J., George A. S., Schafer A. et al. Remdesivir inhibits SARSCoV-2 in human lung cells and chimeric SARS-CoV expressing the SARSCoV-2 RNA polymerase in mice. Cell Reports. 2020; 32 (3): 107940. doi: 10.1016/j.celrep.2020.107940.Pettersson M., Crews C. M. PROteolysis TArgeting Chimeras (PROTACs) — past, present and future. Drug Discov Today Technol. 2019; 31: 15–27. doi: 10.1016/j.ddtec.2019.01.002.Pettersson M., Crews C. M. PROteolysis TArgeting Chimeras (PROTACs) — past, present and future. Drug Discov Today Technol. 2019; 31: 15–27. doi: 10.1016/j.ddtec.2019.01.002.Liu X., Kalogeropulou A. F., Domingos S. et al. Discovery of XL01126: A potent, fast, cooperative, selective, orally bioavailable, and blood-brain barrier penetrant PROTAC degrader of leucine-rich repeat kinase 2. J. Am. Chem. Soc. 2022; 144: 16930–16952. doi: 10.1021/jacs.2c05499.Liu X., Kalogeropulou A. F., Domingos S. et al. Discovery of XL01126: A potent, fast, cooperative, selective, orally bioavailable, and blood-brain barrier penetrant PROTAC degrader of leucine-rich repeat kinase 2. J. Am. Chem. Soc. 2022; 144: 16930–16952. doi: 10.1021/jacs.2c05499.Логинова С. Я., Борисевич С. В., Максимов В. А., Бондарев В. П., Котовская С. К., Русинов В. Л., Чарушин В. Н. Изучение противовирусной активности триазавирина в отношении возбудителя гриппа А (H5N1) в культуре клеток. Антибиотики и химиотер. 2007; 52 (11–12): 18–20.Loginova S. Ya., Borisevich S. V., Maksimov V. A., Bondarev V. P., Kotovskaya S. K., Rusinov V. L., Charushin V. N. Investigation of triazavirin antiviral activity against influenza A virus (H5N1) in cell culture. Antibiot Khimioter = Antibiotics and Chemotherapy. 2007; 52 (11–12): 18–20. (in Russian)Buhrlage S. J., Bates C. A., Rowe S. P. et al. Amphipathic small molecules mimic the binding mode and function of endogenous transcription factors. ACS Chem Biol. 2009 May 15; 4 (5): 335–344. doi: 10.1021/cb900028j.Buhrlage S. J., Bates C. A., Rowe S. P. et al. Amphipathic small molecules mimic the binding mode and function of endogenous transcription factors. ACS Chem Biol. 2009 May 15; 4 (5): 335–344. doi: 10.1021/cb900028j.Qureshi A., Tantray V. G., Kirmani A. R., Ahangar A. G. A review on current status of antiviral siRNA. Rev Med Virol. 2018; 28 (4): e1976. doi: 10.1002/rmv.1976.Qureshi A., Tantray V. G., Kirmani A. R., Ahangar A. G. A review on current status of antiviral siRNA. Rev Med Virol. 2018; 28 (4): e1976. doi: 10.1002/rmv.1976.Haasnoot J., Berkhout B. RNA interference: its use as antiviral therapy. In RNA Towards Medicine. Handbook of experimental pharmacology. Berlin: Springer. 2006; 173: 117–150.Haasnoot J., Berkhout B. RNA interference: its use as antiviral therapy. In RNA Towards Medicine. Handbook of experimental pharmacology. Berlin: Springer. 2006; 173: 117–150.Haasnoot P. C., Cupac D., Berkhout B. Inhibition of virus replication by RNA interference J Biomed Sci. 2003; 10: 607–616. doi: 10.1159/000073526.Haasnoot P. C., Cupac D., Berkhout B. Inhibition of virus replication by RNA interference J Biomed Sci. 2003; 10: 607–616. doi: 10.1159/000073526.Hannon G. J. RNA interference. Nature. 2002; 418: 244–251. doi: 10.1038/418244a.Hannon G. J. RNA interference. Nature. 2002; 418: 244–251. doi: 10.1038/418244a.Ge Q., Filip L., Bai A. et al. Inhibition of influenza virus production in virus-infected mice by RNA interference. Proc Natl Acad Sci U S A. 2004; 101: 8676–8681. doi: 10.1073/pnas.0402486101.Ge Q., Filip L., Bai A. et al. Inhibition of influenza virus production in virus-infected mice by RNA interference. Proc Natl Acad Sci U S A. 2004; 101: 8676–8681. doi: 10.1073/pnas.0402486101.Stoppani E., Bassi I., Dotti S., Lizier M. et al. Expression of a single siRNA against a conserved region of NP gene strongly inhibits in vitro replication of different Influenza A virus strains of avian and swine origin. Antiviral Res. 2015; 120: 16–22. doi: 10.1016/j.antiviral.2015.04.017. Epub 2015 May 16.Stoppani E., Bassi I., Dotti S., Lizier M. et al. Expression of a single siRNA against a conserved region of NP gene strongly inhibits in vitro replication of different Influenza A virus strains of avian and swine origin. Antiviral Res. 2015; 120: 16–22. doi: 10.1016/j.antiviral.2015.04.017. Epub 2015 May 16.Joshi G., Dash P. K., Agarwal A., Sharma S., Parida M. Bifunctional siRNA containing immunostimulatory motif enhances protection against pandemic H1N1 virus infection. Curr Gene Ther. 2015; 15 (5): 492–502. doi: 10.2174/1566523215666150812120547.Joshi G., Dash P. K., Agarwal A., Sharma S., Parida M. Bifunctional siRNA containing immunostimulatory motif enhances protection against pandemic H1N1 virus infection. Curr Gene Ther. 2015; 15 (5): 492–502. doi: 10.2174/1566523215666150812120547.Huang D. T., Lu C-Y., Shao P. L. et al. In vivo inhibition of influenza A virus replication by RNA interference targeting the PB2 subunit via intratracheal delivery. PLoS One. 2017; 12 (4): e0174523. doi: 10.1371/journal.pone.0174523.Huang D. T., Lu C-Y., Shao P. L. et al. In vivo inhibition of influenza A virus replication by RNA interference targeting the PB2 subunit via intratracheal delivery. PLoS One. 2017; 12 (4): e0174523. doi: 10.1371/journal.pone.0174523.White M. D., Farmer M. I., Mirabile I. et al. Single treatment with RNAi against prion protein rescues early neuronal dysfunction and rolongs survival in mice with prion disease. PNAS. 2008; 105 (29): 10238–10243. doi: 10.1073/pnas.0802759105.White M. D., Farmer M. I., Mirabile I. et al. Single treatment with RNAi against prion protein rescues early neuronal dysfunction and rolongs survival in mice with prion disease. PNAS. 2008; 105 (29): 10238–10243. doi: 10.1073/pnas.0802759105.Geisber T., Lee A., Robbins M. et al. Postexposure protection of nonhuman primates against a lethal Ebola virus challenge with RNA interference: a proof-ofconcept study. Lancet. 2010; 375 (9729): 1896–1905. doi: 10.1016/S0140-6736(10)60357-1.Geisber T., Lee A., Robbins M. et al. Postexposure protection of nonhuman primates against a lethal Ebola virus challenge with RNA interference: a proof-ofconcept study. Lancet. 2010; 375 (9729): 1896–1905. doi: 10.1016/S0140-6736(10)60357-1.Seo D., Kim N. Y., Lee J. A. et al. Protection against lethal vaccinia virus infection in mice using an siRNA targeting the A5R gene. Antivir Ther. 2016; 21 (5): 397–404. doi: 10.3851/IMP3022.Seo D., Kim N. Y., Lee J. A. et al. Protection against lethal vaccinia virus infection in mice using an siRNA targeting the A5R gene. Antivir Ther. 2016; 21 (5): 397–404. doi: 10.3851/IMP3022.Романцов М. Г., Галимзянов Х. М., Локтева О. М., Коваленко А. Л., Степанов А. В. Экспериментальная и клинико-лабораторная оценка эффективности комплексной терапии арбовирусных заболеваний. Антибиотики и химиотер. 2012; 57 (7–8): 12–22.Romantsov M. G., Galimzianov Rh. M., Lokteva O. M. et al. Experimental and clinicolaboratory evaluation of complex therapy efficacy in arboviral infections. Antibiot Khimioter = Antibiotics and Chemotherapy. 2012; 57 (7–8): 12–22. (in Russian)Baer A. Protein Phosphatase-1 regulates Rift Valley fever virus replication. A. Baer, N. Shafagati, A. Benedict, et al. Antiviral Res. 2016; Vol.127: P.79–89. doi: 10.1016/j.antiviral.2016.01.007.Baer A. Protein Phosphatase-1 regulates Rift Valley fever virus replication. A. Baer, N. Shafagati, A. Benedict, et al. Antiviral Res. 2016; Vol.127: P.79–89. doi: 10.1016/j.antiviral.2016.01.007.Wolf M. C., Freiberg A. N., Zhang T. et al. A broad-spectrum antiviral targeting entry of enveloped viruses. Proc Natl Acad Sci U S A. 2010; 107 (7): 3157–62. doi: 10.1073/pnas.0909587107.Wolf M. C., Freiberg A. N., Zhang T. et al. A broad-spectrum antiviral targeting entry of enveloped viruses. Proc Natl Acad Sci U S A. 2010; 107 (7): 3157–62. doi: 10.1073/pnas.0909587107.Tong A., Zhang Y., Nemunaitis J. Small interfering RNA for experimental cancer therapy. J Curr Opin Mol Ther. 2005; 7 (2): 114–24.Tong A., Zhang Y., Nemunaitis J. Small interfering RNA for experimental cancer therapy. J Curr Opin Mol Ther. 2005; 7 (2): 114–24.Qiu S., Adema C., Lane T. A computational study of off-target effects of RNA interference. Nucleic Acids Res. 2005; 33 (6): 1834–1847. doi: 10.1093/nar/gki324.Qiu S., Adema C., Lane T. A computational study of off-target effects of RNA interference. Nucleic Acids Res. 2005; 33 (6): 1834–1847. doi: 10.1093/nar/gki324.Wong So C., Klein J. J., Hamilton H. L. et al. Co-Injection of a targeted, reversibly masked endosomolytic polymer dramatically improves the efficacy of cholesterol-conjugated small interfering RNAs in vivo. Nucleic Acid Ther. 2012; 22 (6): 380–390. doi: 10.1089/nat.2012.0389.Wong So C., Klein J. J., Hamilton H. L. et al. Co-Injection of a targeted, reversibly masked endosomolytic polymer dramatically improves the efficacy of cholesterol-conjugated small interfering RNAs in vivo. Nucleic Acid Ther. 2012; 22 (6): 380–390. doi: 10.1089/nat.2012.0389.De Clercq E. Fifty Years in search of selective antiviral drugs. J Med Chem. 2019; 62: 7322–7339. doi: 10.1021/acs.jmedchem.9b00175.De Clercq E. Fifty Years in search of selective antiviral drugs. J Med Chem. 2019; 62: 7322–7339. doi: 10.1021/acs.jmedchem.9b00175.Tompa D. R., Immanuel A., Srikanth S., Kadhirvel S. Trends and strategies to combat viral infections: a review on FDA approved antiviral drugs. Int J Biol Macromol. 2021; 172: 524–541. doi: 10.1016/j.ijbiomac.2021.01.076.Tompa D. R., Immanuel A., Srikanth S., Kadhirvel S. Trends and strategies to combat viral infections: a review on FDA approved antiviral drugs. Int J Biol Macromol. 2021; 172: 524–541. doi: 10.1016/j.ijbiomac.2021.01.076.Chaudhuri S., Symons J. A., Deval J. Innovation and trends in the development and approval of antiviral medicines: 1987–2017 and beyond. Antivir Res. 2018; 155: 76–88. doi: 10.1016/j.antiviral.2018.05.005.Chaudhuri S., Symons J. A., Deval J. Innovation and trends in the development and approval of antiviral medicines: 1987–2017 and beyond. Antivir Res. 2018; 155: 76–88. doi: 10.1016/j.antiviral.2018.05.005.Ашмарин И. П., Лелекова Т. В., Санжиева Л. Ц. Об эффективности ультрамалых доз и концентраций биологически активных соединений. Известия Р. А.Н. 1992; 4: 531–536.Ashmarin I. P., Lelekova T. V., Sanzhieva L. Ts. Ob effektivnosti ul'tramalykh doz i kontsentratsij biologicheski aktivnykh soedinenij. Izvestiya RAN. 1992; 4: 531–536. (in Russian)Бурлакова Е. Б., Конрадова А. А., Мальцева Е. Л. Действие сверхмалых доз биологически активных веществ и низкоинтенсивных физических факторов. Химическая физика. 2003; 22 (2): 390–424.Burlakova E. B., Konradova A. A., Mal'tseva E. L. Dejstvie sverkhmalykh doz biologicheski aktivnykh veshchestv i nizkointensivnykh fizicheskikh faktorov. Khimicheskaya Fizika. 2003; 22 (2): 390–424. (in Russian)Эпштейн О. И. Регуляторные возможности сверхмалых доз. Бюллетень экспериментальной биологии и медицины. 2002; Приложение 4: 8–14.Epshtejn O. I. Regulyatornye vozmozhnosti sverkhmalykh doz. Byulleten' Eksperimental'noj Biologii i Meditsiny. 2002; Prilozhenie 4: 8–14. (in Russian)Эпштейн О. И. Релиз-активность — от феномена до создания новых лекарственных средств. Бюллетень экспериментальной биологии. 2012; 154 (7): 62–67.Epshtejn O. I. Reliz-aktivnost' — ot fenomena do sozdaniya novykh lekarstvennykh sredstv. Byulleten' Eksperimental'noj Biologii. 2012; 154 (7): 62–67. (in Russian)Эпштейн О. И. Феномен релиз-активности и гипотеза «пространственного» гомеостаза. Успехи физиологических наук. 2013; 44 (3): 54–76.Epshtejn O. I. Fenomen reliz-aktivnosti i gipoteza «prostranstvennogo» gomeostaza. Uspekhi Fiziologicheskikh Nauk. 2013; 44 (3): 54–76. (in Russian).

The authors declare that there are no conflicts of interest present.