An innovative drug for the treatment of respiratory infections

The review is devoted to the urgent problem of world health – acute respiratory diseases. This is the most common group of diseases in the human population. Regardless of the type of pathogen, acute respiratory disease manifests itself with similar symptoms, of different duration and severity. More often, respiratory pathogens affect the upper respiratory tract and are limited to the development of catarrhal manifestations with a typical clinical picture in the form of fever, general non-specific/flu-like symptoms and intoxication syndromes. The review presents the results of experimental and clinical studies of a new antiviral drug with antibacterial activity. The drug affects key targets involved in the process of recognizing an infectious pathogen, triggering an immune response and eliminating the pathogen. A series of preclinical studies have demonstrated the efficacy of the drug in viral and mixed viral-bacterial infections. Pharmacological effects of new drug include antiviral, immunotropic, antibacterial and anti-inflammatory activity. The antiviral efficacy of drug components (technologically processed antibodies to IFN-gamma and CD4 receptor) has been previously demonstrated by numerous studies and confirmed by long-term experience with the use of precursors. The new components included in the composition of the drug directly affect the molecules of the major histocompatibility complex and provide not only an increase in the antiviral effect, but also an antibacterial effect. Drug own antibacterial effect was noted, as well as its ability to increase the efficacy of therapy when used in combination with an antibacterial drug. The results of clinical studies have shown the ability to significantly reduce the duration of acute respiratory viral infection and prevent the development of bacterial complications. In the reviewed works, positive data on a favorable safety profile of the drug were obtained. It is considered appropriate to continue clinical studies of the drug in adult and pediatric populations (including children aged 12-18 years).

1. Jamison D. T., Breman J. G., Measham A. R., et al., editors. Disease Control Priorities in Developing Countries. 2nd edition. Washington (DC): The International Bank for Reconstruction and Development/The World Ban, 2006. Accessed November 22 2021. https://www.ncbi.nlm.nih.gov/books/NBK11728/.

2. Thomas M., Bomar P. A. Upper Respiratory Tract Infection. [Updated 2021 Jun 30]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, 2021. Accessed November 22 2021. https://www.ncbi.nlm.nih.gov/books/NBK532961/.

3. Ashworth M., Latinovic R., Charlton J., Cox K., Rowlands G., Gulliford M. Why has antibiotic prescribing for respiratory illness declined in primary care? A longitudinal study using the General Practice Research Database // J Public Health (Oxf). 2004; 26 (3): 268-74. DOI: 10.1093/pubmed/fdh160.

4. Petersen I., Johnson A. M., Islam A., Duckworth G., Livermore D. M., Hayward A. C. Protective effect of antibiotics against serious complications of common respiratory tract infections: retrospective cohort study with the UK General Practice Research Database // BMJ. 2007; 335 (7627): 982. DOI: 10.1136/bmj.39345.405243.BE.

5. Fazylov V. Kh., Sitnikov I. G., Silina Ye. V., Shevchenko S. B., Mozhina L. N., Zamyatina L. L., Yeganyan G. A., Groppa L. G., Korsantiya B. M. Treatment of patients with acute respiratory viral infections and influenza in everyday clinical practice (results of the multicenter international observational study FLU-EE) // Terapevticheskiy arkhiv. 2016; 88 (11): 68-75.

6. Koutsakos M., McWilliam H. E. G., Aktepe T. E., Fritzlar S., Illing P. T., Mifsud N. A., Purcell A. W., Rockman S., Reading P. C., Vivian J. P., Rossjohn J., Brooks A. G., Mackenzie J. M., Mintern J. D., Villadangos J. A., Nguyen T. H. O., Kedzierska K. Downregulation of MHC Class / Expression by Influenza A and B Viruses // Front. Immunol. 2019; 10: 1158. DOI: 10.3389/fimmu.2019.01158.

7. La Gruta N. L.,Turner S. J. T cell mediated immunity to influenza: mechanisms of viral control // Trends Immunol. 2014; 35 (8): 396-402. DOI: https://doi.org/10.1016/j.it.2014.06.004.

8. Thammavongsa V., Kim H. K., Missiakas D., Schneewind O. Staphylococcal manipulation of host immune responses // Nat. Rev. Microbiol. 2015; 13 (9): 529-543. DOI: 10.1038/nrmicro3521.

9. Golubovskaya O. A., Gudzenko O. A., Shestakova I. V., Gaynutdinova T. I.,Levchuk O. O. Post-infectious asthenic syndrome and the possibility of its correction. // Klinicheskaya infektologiya i parazitologiya. 2018; 7 (1): 145-153.

10. Volosovets A. P., Kramarev S. A., Krivopustov S. P., Moroz T. S. Pathogenetic therapy of post-infectious asthenic syndrome in viral diseases // Zdorov'ya Ukraini. 2009; 22 (227): 62-63.

11. Burrell C. J., Howard C. R., Murphy F. A. Fenner and White's Medical Virology. 5th Edition, 2017. 604 pp.

12. Yershov F. I., Garashchenko T. I. Is it possible to control acute respiratory diseases in children? A new look at an old problem // Rossiyskaya rinologiya. 1999; 2: 20-28.

13. Instructions for the medical use of the drug Rafamin. Accessed November 22 2021. https://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=e72e07e8-22a4-4930-a101-c3de9359de88&t=.

14. Teymurazov M. G., Petrova N. V., Karelina Ye. A., Ganina K. K., Tarasov S. A., Epshteyn O. I. Preclinical study of the effectiveness of a new immunotropic drug in the treatment of salmonella infection // Byulleten' sibirskoy meditsiny. 2021; 20 (2): 95-101.

15. Petrova N. V., Yemel'yanova A. G., Tarasov S. A., Kartashova N. P., Glubokova Ye. A. Results of a preclinical study of the effectiveness of an experimental drug based on technologically processed antibodies in models of influenza and mixed viral-bacterial infection // Patogenez. 2020; 18 (4): 55-63.

16. Gorelov A. V., Geppe N. A., Blokhin B. M., Zaytsev A. A., Usenko D. V., Nikolayeva S. V., Nikiforov V. V., Skuchalina L. N., Shamsiyev F. M. Influence of immunomodulatory therapy on the course of acute respiratory infections of viral etiology: a meta-analysis of clinical studies of the efficacy and safety of Ergoferon in the treatment of influenza and other acute respiratory viral infections // Voprosy prakticheskoy pediatrii. 2021; 4 (16): 83-97. DOI: 10.20953/1817-7646-2021-4-83-97.

17. Geppe N. A., Zaplatnikov A. L., Kondyurina Ye. G., Afanas'yeva O. I., Pshenichnaya N. Yu., Blokhin B. M., Kaira A. N., Dondurey Ye. A. Efficacy and safety application of Anaferon for children and Anaferon for the prevention and treatment of influenza and other acute respiratory viral infections: a systematic review and meta-analysis // RMJ. Meditsinskoye obozreniye. 2021; 5 (5): 335-347. DOI: 10.32364/2587-6821-2021-5-5-335-347.

18. Iannello A., Debbeche O., Martin E., Attalah L. B., Samarani S., Ahmad A. Viral strategies for evading antiviral cellular immune responses of the host // J. Leukoc. Biol. 2006; 79 (1): 16-35. DOI: 10.1189/jlb.0705397.

19. Emelyanova A., Petrova N., Gorbunov E., Tarasov S. Highly diluted biologics' perspective in the treatment of bacterial infections // Pharmacology 2020 (British Pharmacological Society). London, UK. December 14-18, 2020. P. 432.

20. Petrova N., Emelyanova A., Gorbunov E., Tarasov S. Induction of dendritic cell maturation by ultra-highly diluted antibodies to MHC class II: in vitro results // Pharmacology 2020 (British Pharmacological Society). London, UK. December 14-18, 2020. P. 483-484.

21. Petrova N., Don E., Emelyanova A., Kardash E., Tarasov S. Screening research of antibacterial potential of selected released-active forms of antibodies / 30th European Congress of Clinical Microbiology and Infectious Diseases. Paris, France. April 18-21, 2020. P. 2966.

22. Khamitov R. F., Nikiforov V. V., Zaytsev A. A., Tragira I. N. Evaluation of the efficacy and safety of a complex antiviral drug based on antibodies in the treatment of adult patients with acute respiratory viral infection // Terapevticheskiy arkhiv. 2022; 94(1): 83-93. DOI: 10.26442/00403660.2022.01.201345.

23. Clinical studies on the drug Rafamin. https://clinicaltrials.gov/ct2/results?cond=&term=MMH-407&cntry=&state=&city=&dist=.