Modern possibilities of etiotropic therapy of influenza: focus on drugs with direct antiviral action

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Influenza is one of the most common diseases and one of the most frequent reasons for visiting primary care physician. The choice of treatment strategy for a patient with influenza depends on a number of factors, such as age, clinical form, nature and severity of infection, presence and type of complications and comorbidities, and the timing of seeking medical care. Basis for successful treatment is the earliest possible detection of the disease and administration of medications that directly target the pathogen. Current article summarizes information on the clinical pharmacology of direct-acting antiviral drugs recommended for the treatment and prevention of influenza in adults.

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Laura Bolieva

North Ossetian State Medical Academy of the Ministry of Healthcare of Russia

编辑信件的主要联系方式.
Email: bolievalz@mail.ru
ORCID iD: 0000-0002-6977-7534

MD, Dr. Sci. (Medicine), professor, head of the Department of pharmacology with clinical pharmacology

俄罗斯联邦, Vladikavkaz

Ella Archegova

North Ossetian State Medical Academy of the Ministry of Healthcare of Russia

Email: ella.ar4egova@yandex.ru

MD, assistant at the Department of pharmacology with clinical pharmacology

俄罗斯联邦, Vladikavkaz

参考

  1. Клинические рекомендации. Грипп у взрослых. Национальная ассоциация специалистов по инфекционным болезням им. академика В.И. Покровского (НАСИБ), общероссийская общественная организация «Российское научное медицинское общество терапевтов». Рубрикатор клинических рекомендаций Минздрава России. 2025. ID: 749_2. Доступ: https://cr.minzdrav.gov.ru/view-cr/749_2 (дата обращения – 21.10.2025). [Clinical guidelines. Influenza in adults. Academician V.I. Pokrovsky National Association of Infectious Disease Specialists, Russian Scientific Medical Society of Internal Medicine. Rubricator of clinical guidelines of the Ministry of Healthcare of Russia. 2025. ID: 749_2. URL: https://cr.minzdrav.gov.ru/view-cr/749_2 (date of access – 21.10.2025) (In Russ.)].
  2. Всемирная организация здравоохранения. Грипп сезонный. 28.02.2025 г. Доступ: https://www.who.int/ru/news-room/fact-sheets/detail/influenza-(seasonal) (дата обращения – 21.10.2025). World Health Organization. Seasonal influenza. February 28, 2025. URL: https://www.who.int/ru/news-room/fact-sheets/detail/influenza-(seasonal) (date of access – 21.10.2025) (In Russ.)].
  3. О состоянии санитарно-эпидемиологического благополучия населения в Российской Федерации в 2024 году. Государственный доклад. М.: Федеральная служба по надзору в сфере защиты прав потребителей и благополучия человека. 2025; 424 с. [On the state of sanitary and epidemiological well-being of the population in the Russian Federation in 2024. State report. Moscow: Federal Service for the Oversight of Consumer Protection and Welfare. 2025; 424 pp. (In Russ.)]. ISBN: 978-5-7508-2350-5.
  4. Hulo C, de Castro E, Masson P, Bougueleret L, Bairoch A, Xenarios I, Le Mercier P. ViralZone: A knowledge resource to understand virus diversity. Nucleic Acids Res. 2011;39(Database issue):D576–82. PMID: 20947564. PMCID: PMC3013774. https://doi.org/10.1093/nar/gkq901
  5. Орлова Н.В. Грипп. Диагностика, стратегия выбора противовирусных препаратов. Медицинский совет. 2017;(20):80–86. [Orlova NV. Influenza. Diagnostics, strategy for selection of anti-virals. Meditsinskiy sovet = Medical Council. 2017;(20):80–86 (In Russ.)]. EDN: YLOGPI. https://doi.org/10.21518/2079-701X-2017-20-80-86
  6. Литусов Н.В. Вирусы гриппа. Иллюстрированное учебное пособие. Екатеринбург: УГМУ. 2018; 22 с. Доступ: https://elib.usma.ru/bitstream/usma/1058/1/UMK_2018_010.pdf (дата обращения – 21.10.2025). [Litusov NV. Influenza viruses. Illustrated textbook. Yekaterinburg: Ural State Medical University. 2018; 22 pp. (In Russ.)]. URL: https://elib.usma.ru/bitstream/usma/1058/1/UMK_2018_010.pdf (date of access – 21.10.2025) (In Russ.)].
  7. Каира А.Н., Лавров В.Ф. Грипп. Учебное пособие. М.: РМАНПО. 2020; 107 с. [Kaira AN, Lavrov VF. Influenza. Study guide. Moscow: Russian Medical Academy of Continuous Professional Education. 2020; 107 pp. (In Russ.)]. EDN: SMFYJP. ISBN: 978-5-7249-3182-3.
  8. Сологуб Т.В. Грипп в современных условиях: противовирусная терапия прямого действия. Медицинский совет. 2015;(4):36–45. [Sologub TV. Influenza in today: Direct-acting antiviral therapy. Meditsinskiy sovet = Medical Council. 2015;(4):36–45 (In Russ.)]. EDN: TPPTXX.
  9. Ларина В.Н., Чуланов В.П. Новые возможности в лечении пациентов с гриппом: препарат балоксавир марбоксил. Лечебное дело. 2020;(4):38–47. [Larina VN, Chulanov VP. New opportunities for the treatment of patients with influenza: Baloxavir marboxil. Lrechebnoe delo = General Medicine. 2020;(4):38–47 (In Russ.)]. EDN: SNTBHJ. https://doi.org/10.24412/2071-5315-2020-12269
  10. Государственный реестр лекарственных средств Минздрава России. Инструкции по медицинскому применению лекарственных препаратов с МНН осельтамивир, занамивир, балоксавир марбоксил, умифеновир, риамиловир, энисамия йодид. Доступ: https://grls.minzdrav.gov.ru/ (дата обращения – 21.10.2025). [State Register of Medicines of the Ministry of Healthcare of Russia. Instructions for medical use of medicinal products with INN oseltamivir, zanamivir, baloxavir marboxil, umifenovir, riamilovir, and enisamium iodide. URL: https://grls.minzdrav.gov.ru/ (date of access – 21.10.2025) (In Russ.)].
  11. Kumar G, Sakharam KA. Tackling influenza A virus by M2 ion channel blockers: Latest progress and limitations. Eur J Med Chem. 2024;267:116172. PMID: 38330869. https://doi.org/10.1086/518936
  12. Deyde VM, Xu X, Bright RA, Shaw M, Smith CB, Zhang Y et al. Surveillance of resistance to adamantanes among influenza A(H3N2) and A(H1N1) viruses isolated worldwide. J Infect Dis. 2007;196(2):249–57. PMID: 17570112. https://doi.org/10.1086/518936
  13. Dong G, Peng C, Luo J, Wang C, Han L, Wu B et al. Adamantane-resistant influenza a viruses in the world (1902–2013): Frequency and distribution of M2 gene mutations. PLoS ONE 2015;10(3):e0119115. PMID: 25768797. PMCID: PMC4358984. https://doi.org/10.1371/journal.pone.0119115
  14. Чернова Т.М., Тимченко В.М. Противовирусные препараты в лечении гриппа. Terra Medica. 2011;(1):10–14. [Chernova TM, Timchenko VM. Antiviral drugs in the treatment of influenza. Terra Medica. 2011;(1):10–14 (In Russ.)]. EDN: NUGCUN.
  15. Hayden FG, Atmar RL, Schilling M, Johnson C, Poretz D, Paar D, Huson L et al. Use of the selective oral neuraminidase inhibitor oseltamivir to prevent influenza. N Engl J Med. 1999;341(18):1336–43. PMID: 10536125. https://doi.org/10.1056/NEJM199910283411802
  16. Jefferson T, Jones M, Doshi P, Spencer EA, Onakpoya I, Heneghan CJ. Oseltamivir for influenza in adults and children: Systematic review of clinical study reports and summary of regulatory comments. BMJ. 2014;348:g2545. PMID: 24811411. PMCID: PMC3981975. https://doi.org/10.1136/bmj.g2545
  17. Dobson J, Whitley RJ, Pocock S, Monto AS. Oseltamivir treatment for influenza in adults: A meta analysis of randomised controlled trials. Lancet. 2015;385(9979):1729–37. PMID: 25640810. https://doi.org/10.1016/S0140-6736(14)62449-1
  18. Doll MK, Winters N, Boikos C, Kraicer-Melamed H, Gore G, Quach C. Safety and effectiveness of neuraminidase inhibitors for influenza treatment, prophylaxis, and outbreak control: A systematic review of systematic reviews and/or meta-analyses. J Antimicrob Chemother. 2017;72(11):2990–3007. PMID: 28961794. https://doi.org/10.1093/jac/dkx271
  19. Hsu J, Santesso N, Mustafa R, Brozek J, Chen YL, Hopkins JP et al. Antivirals for treatment of influenza: A systematic review and meta-analysis of observational studies. Ann Intern Med. 2012;156(7):512–24. PMID: 22371849. PMCID: PMC6679687. https://doi.org/10.7326/0003-4819-156-7-201204030-00411
  20. Okoli GN, Harmony EO, Beck CR, Nguyen-Van-Tam JS. Use of neuraminidase inhibitors for rapid containment of influenza: A systematic review and meta-analysis of individual and household transmission studies. PLoS One. 2014;9(12):e113633. PMID: 25490762. PMCID: PMC4260958. https://doi.org/10.1371/journal.pone.0113633
  21. Фесенко О.В. Актуальные вопросы использования осельтамивира при гриппе. РМЖ. 2021;29(4):63–66. [Fesenko OV. Topical issues concerning oseltamivir use in influenza. Russkiy meditsinskiy zhurnal = Russian Medical Journal. 2021;29(4):63–66 (In Russ.)]. EDN: HFPPOO.
  22. Hama R, Bennett CL. The mechanisms of sudden-onset type adverse reactions to oseltamivir. Acta Neurol Scand. 2017;135(2):148–60. PMID: 27364959. PMCID: PMC5201449. https://doi.org/10.1111/ane.12629
  23. Han N, Oh JM, Kim IW. Assessment of adverse events related to antiinfluenza neuraminidase inhibitors using the FDA adverse event reporting system and online patient reviews. Sci Rep. 2020;10(1):3116. PMID: 32080337. PMCID: PMC7033147. https://doi.org/10.1038/s41598-020-60068-5
  24. Cooper NJ, Sutton AJ, Abrams KR, Wailoo A, Turner D, Nicholson KG. Effectiveness of neuraminidase inhibitors in treatment and prevention of influenza A and B: Systematic review and meta-analyses of randomised controlled trials. BMJ. 2003;326(7401):1235. PMID: 12791735. PMCID: PMC161558. https://doi.org/10.1136/bmj.326.7401.1235
  25. Bragstad K, Hungnes O, Litleskare I, Nyrerod HC, Dorenberg DH, Hauge SH. Community spread and late season increased incidence of oseltamivir-resistant influenza A(H1N1) viruses in Norway 2016. Influenza Other Respir Viruses. 2019;13(4):372–81. PMID: 30834715. PMCID: PMC6586177. https://doi.org/10.1111/irv.12637
  26. Fukao K, Ando Y, Noshi T, Kitano M, Noda T, Kawai M et al. Baloxavir marboxil, a novel cap-dependent endonuclease inhibitor potently suppresses influenza virus replication and represents therapeutic effects in both immunocompetent and immunocompromised mouse models. PLoS One 2019;14(5):e0217307. PMID: 31107922. PMCID: PMC6527232. https://doi.org/10.1371/journal.pone.0217307
  27. Hayden FG, Sugaya N, Hirotsu N, Lee N, de Jong MD, Hurt AC et al.; Baloxavir Marboxil Investigators Group. Baloxavir marboxil for uncomplicated influenza in adults and adolescents. N Engl J Med. 2018;379(10):913–23. PMID: 30184455. https://doi.org/10.1056/NEJMoa1716197.
  28. Ison MG, Portsmouth S, Yoshida Y, Shishido T, Hayden F, Uehara T. LB16. Phase 3 trial of baloxavir marboxil in high-risk influenza patients (CAPSTONE-2 study). Open Forum Infect Dis. 2018;5(1):764–65. https://doi.org/10.1093/ofid/ofy229.2190
  29. Kuo YC, Lai CC, Wang YH, Chen CH, Wang CY. Clinical efficacy and safety of baloxavir marboxil in the treatment of influenza: A systematic review and meta-analysis of randomized controlled trials. J Microbiol Immunol Infect. 2021;54(5):865–75. PMID: 34020891. https://doi.org/10.1016/j.jmii.2021.04.002
  30. Булгакова В.А., Поромов А.А., Грекова А.И., Пшеничная Н.Ю., Селькова Е.П., Львов Н.И. с соавт. Фармакоэпидемиологическое исследование течения гриппа и других ОРВИ в группах риска. Терапевтический архив. 2017;89(1):62–71. [Bulgakova VA, Poromov AA, Grekova AI, Pshenichnaya NYu, Selkova EP, Lvov NI et al. Pharmacoepidemiological study of the course of influenza and other acute respiratory viral infections in risk groups. Terapevticheskiy arkhiv = Therapeutic Archive. 2017;89(1):62–71 (In Russ.)]. EDN: XXELPN. https://doi.org/10.17116/terarkh201789162-71
  31. Киселев О.И., Малеев В.В., Деева Э.Г., Ленева И.А., Селькова Е.П., Осипова Е.А. с соавт. Клиническая эффективность препарата Арбидол (умифеновир) в терапии гриппа у взрослых: промежуточные результаты многоцентрового двойного слепого рандомизированного плацебо контролируемого исследования АРБИТР. Терапевтический архив. 2015;91(1):88–96. [Kiselev OI, Maleev VV, Deeva EG, Leneva IA, Selkova EP, Osipova EA et al. Clinical efficacy of Аrbidol (umifenovir) in the therapy of influenza in adults: Preliminary results of the multicenter double-blind randomized placebo-controlled study ARBITR. Terapevticheskiy arkhiv = Therapeutic Archive. 2015;91(1):88–96 (In Russ.)]. EDN: UABVON. https://doi.org/10.17116/terarkh201587188-96
  32. Пшеничная Н.Ю., Булгакова В.А., Львов Н.И., Поромов А.А., Селькова Е.П., Грекова А.И. с соавт. Клиническая эффективность умифеновира при гриппе и ОРВИ (исследование АРБИТР). Терапевтический архив. 2019;91(3):56–63. [Pshenichnaya NYu, Bulgakova VA, Lvov NI, Poromov AA, Selkova EP, Grekova AI et al. Clinical efficacy of umifenovir in influenza and ARVI (study ARBITR). Terapevticheskiy arkhiv = Therapeutic Archive. 2019;91(3):56–63 (In Russ.)]. EDN: ZDFPAT. https://doi.org/10.26442/00403660.2019.03.000127
  33. Karpenko I, Deev S, Kiselev O, Charushin V, Rusinov V, Ulomsky E, Deeva E et al. Antiviral properties, metabolism, and pharmaco kinetics of a novel azolo-1,2,4-triazine-derived inhibitor of influenza A and B virus replication. Antimicrob Agents Chemother. 2010;54(5):2017–22. PMID: 20194696. PMCID: PMC2863629. http://doi.org/10.1128/AAC.01186-09
  34. Chupakhin ON, Rusinov VL, Varaksin MV, Ulomskiy EN, Savateev KV, Butorin II et al. Triazavirin – a novel effective antiviral drug. Int J Mol Sci. 2022;23(23):14537. PMID: 36498864. PMCID: PMC9738222. https://doi.org/10.3390/ijms232314537
  35. Киселев О.И., Деева Э.Г., Мельникова Т.И., Козелецкая К.Н., Киселев А.С., Русинов В.Л. с соавт. Новый противовирусный препарат Триазавирин. Результаты II фазы клинического исследования. Вопросы вирусологии. 2012;57(6):9–13. [Kiselev OI, Deyeva EG, Melnicova TI, Kozeletskaia KN, Kiselev AS, Rusinov VL et al. A new antiviral drug triazavirin: Results of phase II clinical trial. Voprosy virusologii = Problems of Virology. 2012;57(6):9–13 (In Russ.)]. EDN: PUJEUV.
  36. Boltz D, Peng X, Muzzio M, Dash P, Thomas PG, Margitich V. Activity of enisamium, an isonicotinic acid derivative, against influenza viruses in differentiated normal human bronchial epithelial cells. Antivir Chem Chemother. 2018;26:2040206618811416. PMID: 30466301. PMCID: PMC6961345. https://doi.org/10.1177/2040206618811416
  37. Walker AP, Fan H, Keown JR, Margitich V, Grimes JM, Fodor E, Te Velthuis AJW. Enisamium is a small molecule inhibitor of the influenza A virus and SARS-CoV-2 RNA polymerases. bioRxiv [Preprint]. 2020:2020.04.21.053017. PMID: 32511388. PMCID: PMC7263517. https://doi.org/10.1101/2020.04.21.053017
  38. Карева Е.Н., Федотчева Т.А., Семейкин А.В., Кочина Н.А., Краснощок Е.В., Шимановский Н.Л. Энисамия йодид – влияние на ключевые компоненты воспалительного процесса при ОРВИ. Терапевтический архив. 2022;94(11):1262–1267. [Kareva EN, Fedotcheva TA, Semeikin AV, Kochina NA, Krasnoshchok EV, Shimanovskii NL. The mechanisms of anti-inflammatory action of enisamium iodide. Terapevticheskiy arkhiv = Therapeutic Archive. 2022;94(11):1262–1267. EDN: NOKRCZ. https://doi.org/10.26442/00403660.2022.11.201961
  39. Лиознов Д.А. Карнаухова Е.Ю., Зубкова Т.Г., Шахланская Е.В. Оценка эффективности схемы лечения ОРВИ, включающей этиотропную (энисамия йодид) и симптоматическую терапию. Терапевтический архив. 2020;92(3):50–55. [Lioznov DA, Karnaukhova EJ, Zubkova TG, Shakhlanskaya EV. Evaluation of the effectiveness of ARVI treatment regimen including etiotropic (enisamium iodide) and symptomatic treatment. Terapevticheskiy arkhiv = Therapeutic Archive. 2020;92(3):50–55 (In Russ.)]. EDN: NXCEXE. https://doi.org/10.26442/00403660.2020.03.000572
  40. Баранов И.И., Арсланян К.Н., Нестерова Л.А. Грипп у беременных. Акушерство и гинекология. Новости. Мнения. Обучение. 2018;(2):42–51. [Baranov II, Arslanyan KN, Nesterova LA. Influenza in pregnant women. Akusherstvo i ginekologiya. Novosti. Mneniya. Obuchenie = Obstetrics and Gynecology. News. Opinions. Training. 2018;(2):42–51 (In Russ.)]. EDN: XPQBWP.
  41. Арчегова Э.Г. Болиева Л.З. Применение лекарственных средств в первом триместре беременности: фармакоэпидемиологическое исследование. Владикавказский медико-биологический вестник. 2015;21(31):45–47. [Archegova EG, Bolieva LZ. The use of drugs in the first trimester of pregnancy: Pharmacoepidemiologic study. Vladikavkazskiy mediko-biologicheskiy vestnik = Vladikavkaz Medico-Biological Bulletin. 2015;21(31):45–47 (In Russ.)]. EDN: VQDAHH. https://doi.org/10.12737/17245
  42. Арчегова Э.Г. Болиева Л.З. Применение лекарственных средств во втором триместре беременности: фармакоэпидемиологическое исследование. Современные проблемы науки и образования. 2015;(4):424. [Archegova EG, Bolieva LZ. The use of drugs in the second trimester of pregnancy: Pharmacoepidemiologic study. Sovremennyye problemy nauki i obrazovaniya = Modern Problems of Science and Education. 2015;(4):424 (In Russ.)]. EDN: UDWZXV.
  43. Арчегова Э.Г. Болиева Л.З. Применение лекарственных средств в третьем триместре беременности: фармакоэпидемиологическое исследование. Фундаментальные исследования. 2015;(1–10):2001–2004. [Archegova EG, Bolieva LZ. The use of drugs in the third trimester of pregnancy: Pharmacoepidemiologic study. Fundamental’nyye issledovaniya = Fundamental Research. 2015;(1–10):2001–2004 (In Russ.)]. EDN: UBPUNP.

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