Immunological mechanisms of the drug Cytovir®-3 action as the basis of the prevention of acute respiratory viral infections and influenza

Abstract

Introduction. Influenza viruses and other acute respiratory viral infections (ARVI) cause massive outbreaks of infectious diseases quite often becoming epidemic nature. The economic and social damage done to the health of the population by these infections and related complications is enormous. It is quite naturally, many research teams are persistently looking for ways and means of solving this serious problem. The complex preparation Cytovir®-3 in the form of capsules has been used for 20 years for the prevention and early pathogenetic treatment of influenza and ARVI. The study of the mechanism of anti-infectious protection is one of the main tasks in the development of a antiviral medicinal product with both direct and indirect effects.

The article presents the results of an open non-randomized clinical study of the safety and tolerability of the drug Cytovir®-3 capsules in healthy volunteers aged 18 to 30 years with a prolonged course of taking the drug with the study of immunological mechanisms of action

Aim of the study - to investigate the immunological mechanisms of action and safety of Cytovir®-3 capsules in healthy volunteers with a prolonged course of administration.

Material and methods. The article presents the results of an open, non-randomized clinical study of the safety and tolerability of Cytovif®-3 capsules in 21 healthy volunteers aged 18 to 30 years. The duration of the course of taking Cytovir®-3 was 14 days, 1 capsule 3 times a day. An in-depth examination of the volunteers was carried out at the screening stage, on the 5th day of taking the drug and after the 14-day course. Safety and tolerance were assessed according to the data of clinical examination with fixation of vital signs, as well as by studying the dynamics of clinical and biochemical blood tests, general urine analysis and indicators of the body’s immunological reactivity.

Results. In the course of the clinical study the activating effect of the drug on the indicators of stimulated oxidative NBT activity and the level of lysosomal cationic proteins, the phagocytic index, as well as the dynamics of secretory IgA (sIgA) was noted. 4 Cases of adverse events (headache and itching) were registered in 3 (14.3 %) participants, they were regarded as mild and unlikely to be related to the drug intake.

Conclusion. The studied scheme of the prolonged course of taking the drug Cytovir®-3 capsules showed the activity of the drug in relation to the microbicidal parameters of the cells of innate immunity (functional activity of monocytes, neutrophils, as well as the level of sIgA), the fluctuations of which were significant and localized within the limits of the adaptive response norm, which indicates an increase in the body’s immunoresistance after the course and reveals the mechanisms of the preventive action of the drug was shown a high level of safety and good tolerance in assessing the effect on the vital functions of the body, instrumental, laboratory general clinical and immunological indicators.

Keywords:antiviral activity; Cytovir-3®; healthy volunteers; prophylactic action; innate immunity; safety

For citation: Ruleva A.A., Popova V.V., Lyovina A.V., Krasnov A.A., Petlenko S.V. Immunological mechanisms of the drug Cytovir®-3 action as the basis of the prevention of acute respiratory viral infections and influenza. Immu-nologiya. 2021; 42 (2): 148-58. DOI: https://doi.org/10.33029/0206-4952-2021-42-2-148-158 (in Russian)

Funding. The study had no sponsor support.

Conflict of interests. The authors declare no conflict of interests.

References

1. Andryukov B.G., Somova L.M., Drobot E.I., Matosova E.V. Protective strategies of neutrophilic granulocytes against pathogenic bacteria. Zdorov’e. Meditsinskaya ekologiya. Nauka. 2017; 1 (68): 4–18. (in Russian)

2. Aralova E.V., Kuprina N.P., Pokataeva N.I., Kokoreva S.P., Sakharova L.A. Clinical and immunological features of acute bronchitis in children. Detskie infektsii. 2008; 3: 28–30. (in Russian)

3. Duda A.K., Kotsyubaylo L.P. Modern immunotropic therapy of patients with coronavirus infections. Aktual’naya infektologiya. 2016; 3 (12): 33–7. (in Russian)

4. Erofeeva M.K., Pozdnyakova M.G., Golovacheva E.G. Comparative clinical efficacy of drugs for non-specific prophylaxis of influenza and ARVI in children during the period of seasonal rise in morbidity. Zhurnal infektologii. 2020; 12 (2): 63–70. (in Russian)

5. Kim K.F. The influence of synthetic analogs of thymus peptides on the production of cytokines and phagocytic activity of peripheral blood cells: Diss. Moscow, 2004. (in Russian)

6. Petlenko S.V., Osidak L.V., Smirnov V.S., Stukan’ N.I., Afanas’eva O.I., Golovacheva E.G. Comparative clinical and laboratory effectiveness of drugs for the pathogenetic treatment of acute respiratory viral infections. Voprosy virusologii. 2016; 61 (6): 263–9. (in Russian)

7. Petlenko S.V., Smirnov V.S., Rudenko V.V. The course of in-hospital coronavirus infection (COVID-19) against the background of prophylactic and therapeutic intake of peptide immunotropic drugs as part of complex therapy. Folmuly farmatsii [Pharmacy Formulas]. 2020; 2 (3): 8–13. (in Russian)

8. Pigarevsky V.E. Lysosomal cation test: Methodical recommendations. Moscow, 1979. (in Russian)

9. Savlevich E.L., Brodovskaya O.B., Remizova I.I., Chistyakova G.N., Ishchenko A.M., Simbirtsev A.S. Clinical and immunological efficacy of a new aerosol form of recombinant interferon α2b in the treatment of patients with acute nasopharyngitis. Tsitokiny i vospalenie. 2010; 9 (1): 49–56. (in Russian)

10. Smirnov V.S., Petlenko S.V., Osidak L.V., Stukan’ N.I., Levina A.V., Malakhova E.A., Meshkova M.E. Comparative clinical and laboratory evaluation of various drugs for etiopathogenetic therapy of influenza and ARVI. Rossiyskiy immunologicheskiy zhurnal. 2017; 11 (20) (2): 230–1. (in Russian)

11. Smirnov V.S. Cytovir-3 increases the activity of humoral factors of the innate immune system. Rossiyskiy allergologicheskiy zhurnal. 2012; 1 (1): 293–4. (in Russian)

12. Smirnov V.S., Zarubaev V.V., Petlenko S.V. Biology of pathogens and control of influenza and SARS. Saint Petersburg, 2020: 338 p. (in Russian)

13. Smirnov V.S., Petlenko S.V. Influenza and acute respiratory viral infections. Saint Petersburg: Gippokrat, 2019: 248 p. (in Russian)

14. Smirnov V.S., Totolyan A.A. Some possibilities of immunotherapy for coronavirus infection. Infektsiya i immunitet. 2020; 10 (3): 446–58. (in Russian)

15. Tikhomirova A.R., Ruleva A.A. Clinical and immunological efficacy of a domestic immunotropic drug in children with acute respiratory infections with broncho-obstructive syndrome. Immunologiya. 2020; 41 (3): 249–55. (in Russian)

16. Filinyuk O.V., Zemlyanaya N.A., Strelis A.K., Urazova O.I., Voronkova O.V., Shevtsova N.M., Esimova I.E. Cytochemical and microbicidal activity of blood phagocytes in patients with pulmonary tuberculosis. Byulleten’ sibirskoy meditsiny. 2007; 1: 62–7. (in Russian)

17. Chesnokova N.P., Ponukalina E.V., Nevvazhay T.A., Zhevak T.N., Bizenkova M.N. Lecture 3. Features of the structure, function and metabolism of blood monocytes and mononuclear-phagocytic system of tissues. Mezhdunarodniy zhurnal prikladnykh i fundamental’nykh issledovaniy. 2015; 4-2: 290–2. (in Russian)

18. Shipitsyn K.S., Ogarkov P.I., Smirnov V.S., Zhogolev S.D., Zhogolev K.D. Prevention of acute respiratory viral infections and pneumonia in an organized team. Epidemiologiya i infektsionnye bolezni. 2010; 1: 57–61. (in Russian)

19. Agha N.H., Baker F.L., Kunz H.E., Spielmann G., Mylabathula P.L., Rooney B.V., Mehta S.K., Pierson D.L., Laughlin M.S., Markofski M.M., Crucian B.E., Simpson R.J. Salivary antimicrobial proteins and stress biomarkers are elevated during a 6-month mission to the International Space Station. J. Appl. Physiol. 2020; 128 (2): 264–75.

20. Cooper G.E., Pounce Z.C., Wallington J.C., Bastidas-Legarda L.Y., Nicholas B., Chidomere C., Robinson E.C., Martin K., Tocheva A.S., Christodoulides M., Djukanovic R., Wilkinson T.M., Staples K.J. Viral inhibition of bacterial phagocytosis by human macrophages: redundant role of CD36. PLoS One. 2016; 11 (10): e0163889.

21. García L.F. Immune response, inflammation, and the clinical spectrum of COVID-19. Front. Immunol. 2020; 11: 1441.

22. Kobayashi S.D., Malachowa N., DeLeo F.R. Neutrophils and bacterial immune evasion. J. Innate Immun. 2018; 10 (5–6): 432–41.

23. Levy O. Antimicrobial proteins and peptides: anti-infective molecules of mammalian leukocytes. J. Leukoc. Biol. 2004; 76 (5): 909–25.

24. Ma H., Zeng W., He H., Zhao D., Jiang D., Zhou P., Cheng L., Li Y., Ma X., Jin T. Serum IgA, IgM, and IgG responses in COVID-19. Cell. Mol. Immunol. 2020; 17 (7): 773–5.

25. Okba N.M.A., Müller M.A., Li W., Wang C., Geurtsvan-Kessel C.H., Corman V.M., Lamers M.M., Sikkema R.S., de Bruin E., Chandler F.D., Yazdanpanah Y., Le Hingrat Q., Descamps D., Houhou-Fidouh N., Reusken C.B.E.M., Bosch B.J., Drosten C., Koopmans M.P.G., Haagmans B.L. Severe acute respiratory syndrome coronavirus 2-specific antibody responses in coronavirus disease patients. Emerg. Infect. Dis. 2020; 26 (7): 1478–88.

26. Rajasekaran G., Dinesh Kumar S., Nam J., Jeon D., Kim Y., Lee C.W., Park I.S., Shin S.Y. Antimicrobial and anti-inflammatory activities of chemokine CXCL14-derived antimicrobial peptide and its analogs. Biochim. Biophys. Acta Biomembr. 2019; 1861 (1): 256–67.

27. Saito S., Sano K., Suzuki T., Ainai A., Taga Y., Ueno T., Tabata K., Saito K., Wada Y., Ohara Y., Takeyama H., Odagiri T., Kageyama T., Ogawa-Goto K., Multihartina P., Setiawaty V., Pangesti K.N.A., Hasegawa H. IgA tetramerization improves target breadth but not peak potency of functionality of anti-influenza virus broadly neutralizing antibody. PLoS Pathog. 2019; 15 (1): e1007427.

28. Smirnov V.S., Saveliev S.A., Petlenko S.V., Redlich G., Erofeeva M.K., Lyovina A.V., Zavialova N.I. Comparative efficacy and safety of preventive treatment with cytovir-3 and arbidol in children during seasonal outbreak of respiratory viral infection (an open-label randomized clinical study). Russian Journal of Infection and Immunity. 2019; 9 (2): 273–8. DOI: https://doi.org/10.15789/2220-7619-2019-2-273-278

29. Smiyan O.I., Smiian-Horbunova K.O., Bynda T.P., Loboda A.M., Popov S.V., Vysotsky I.Y., Moshchych O.P., Vasylieva O.G., Manko Y.A., Ovsianko O.L., Kolesnikova M.V., Dolgova N.O., Aleksakhina T.O., Al-Rawashdeh B. Optimization of the treatment of rotavirus infection in children by using bacillus clausii. Wiad. Lek. 2019; 72 (7): 1320–3.

30. Teng T.S., Ji A.L., Ji X.Y., Li Y.Z. Neutrophils and Immunity: From Bactericidal Action to Being Conquered. J. Immunol. Res. 2017; 2017: 9671604. Epub 2017 Feb 19. DOI: https://doi.org/10.1155/2017/9671604

31. Varadhachary A., Chatterjee D., Garza J., Garr R.P., Foley C., Letkeman A.F., Dean J., Haug D., Breeze J., Traylor R., Malek A., Nath R., Linbeck L. Salivary anti-SARS-CoV-2 IgA as an accessible biomarker of mucosal immunity against COVID-19. medRxiv. 2020; Aug 11: 2020.08.07.20170258. DOI: https://doi.org/10.1101/2020.08.07.20170258

32. Wiesner J., Vilcinskas A. Antimicrobial peptides: the ancient arm of the human immune system. Virulence. 2010; 1 (5): 440–64.

33. Xingyuan C., Chen Q. Serum BPI as a novel biomarker in asthma. Allergy Asthma Clin. Immunol. 2020; 16: 50.

34. Yamamoto Y., Saruta J., Takahashi T., To M., Shimizu T., Hayashi T., Morozumi T., Kubota N., Kamata Y., Makino S., Kano H., Hemmi J., Asami Y., Nagai T., Misawa K., Kato S., Tsukinoki K. Effect of ingesting yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 on influenza virus-bound salivary IgA in elderly residents of nursing homes: a randomized controlled trial. Acta Odontol. Scand. 2019; 77 (7): 517–24.

All articles in our journal are distributed under the Creative Commons Attribution 4.0 International License (CC BY 4.0 license)


JOURNALS of «GEOTAR-Media»