Experimental study of the effect of the active substance of miramistin® on the infectious activity of SARS-CoV-2 in vitro


DOI: https://dx.doi.org/10.18565/epidem.2022.12.3.91-6

Leneva I.A., Gracheva A.V., Korchevaya E.R., Smirnova D.I., Faizuloev E.V.

I.I. Mechnikov Research Institute of Vaccines and Sera, Moscow, Russia
Objective. To investigate and laboratorily confirm the effect of miramistin® (benzyldimethyl-myristoylamine-propylammonium (BMPA)) on the infectious activity of SARS-CoV-2 in vitro.
Materials and methods. The investigators used cultured Vero CCL-81 cells derived from the monkey kidney and the laboratory SARS-CoV-2 strain Dubrovka. They applied cultural, virological, molecular biological, and statistical studies. All experiments used the original pharmaceutical substance BMPA chloride (OOO «INFAMED», Russia).
Results. The study of BMPA cytotoxicity in the cultured cells indicated that its CTD50 was 0,0091±0,002%, and the MTC was 0.005%. The original drug had a pronounced virucidal activity against SARS-CoV-2, by completely suppressing its infectivity at a concentration of 0.005% or higher. An additional experiment identifying the result by virus titration and in the virus-specific real-time RT-PCR assay confirmed complete virus inactivation in the range of non-toxic concentrations of 0.01–0.0025%.
Conclusion. The original pharmaceutical substance BMPA chloride in vitro exhibits a pronounced virucidal activity at the concentrations corresponding to that of the active substance in miramistin (0.01%), and even at lower concentrations (0.005 and 0.0025%).

Literature


1. ICTV (International Committee on Taxonomy of Viruses). https://talk.ictvonline.org/ictv-reports/ictv_9th_report/positive-sense-rna-viruses-2011/w/posrna_viruses/222/coronaviridae


2. Guo Y.R., Cao Q.D., Hong Z.S., Tan Y.Y., Chen S.D., Jin H.J. et al. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak – an update on the status. Mil. Med. Res. 2020; 7(1): 11. doi: 10.1186/s40779-020-00240-0.


3. Khan F.A. The role of Selectivity of the SARS-CoV-2 Virus for Human Genetic Profiles in Susceptibility and Resistance to COVID-19. New Microbes New Infect. 2020; 36: 100697. https://doi.org/10.1016/j.nmni.2020.100697


4. Russell C.D., Millar J.E., Baillie J.K. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet 2020; 395(10223): 473–5. doi: 10.1016/S0140-6736(20)30317-2.


5. Yang X., Yu Y., Xu J., Shu H., Xia J., Liu H. et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir. Med. 2020; 8(5): 475–81. doi: 10.1016/S2213-2600(20)30079-5


6. Liu K., Fang Y.Y., Deng Y., Liu W., Wang M.F., Ma J.P. Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province. Chin. Med. J. (Engl.). 2020; 133(9): 1025–31. doi: 10.1097/CM9.0000000000000744


7. Oran D.P., Topol E.J. Prevalence of Asymptomatic SARS-CoV-2 Infection: A Narrative Review. Annals of internal medicine 2020; 173(5), 362–7. doi: 10.7326/M20-3012


8. Abduljalil J.M., Abduljalil B.M. Epidemiology, genome, and clinical features of the pandemic SARS-CoV-2: a recent view. New Microbes New Infect. 2020; 35: 100672. doi: 10.1016/j.nmni.2020.100672


9. Wu Z., McGoogan J.M. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA 2020; 323(13): 1239–42. doi:10.1001/jama.2020.2648 32091533.


10. Harrison S.L., Fazio-Eynullayeva E., Lane D.A., Underhill P. Comorbidities associated with mortality in 31,461 adults with COVID-19 in the United States: A federated electronic medical record analysis. PLoS Med. 2020; 17(9): e1003321. doi: 10.1371/journal.pmed.1003321


11. Liu Y., Sun W., Li J., Chen L., Wang Y., Zhang L., Yu L. Clinical features and progression of acute respiratory distress syndrome in coronavirus disease 2019. medRxiv 2020. https://doi.org/10. 1101/2020.02.17.20024166


12. Sanders J.M., Monogue M.L., Jodlowski T.Z., Cutrell J.B. Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review. JAMA 2020; 323(18): 1824–36. doi: 10.1001/jama.2020.6019


13. Дунаевский А.М., Кириченко И.М. Местная терапия инфекционно-воспалительных заболеваний респираторной системы. Лечащий врач 2014; (10): 1–3. www.lvrach.ru


Dunayevsky A.M., Kirichenko I.M. [Local therapy of infectious and inflammatory diseases of the respiratory system]. The Attending Physician 2014; (10): 1–3. (In Russ.). www.lvrach.ru


14. Шабалдина Е.В., Рязанцев С.В., Шабалдин А.В. Эффективность применения мирамистина у детей раннего и дошкольного возраста с гипертрофией миндалин лимфоидного глоточного кольца, с рецидивирующими острыми респираторными инфекциями и сенсибилизацией к Streptococcus pyogenes. Педиатрия. Журнал им. Г.Н. Сперанского 2015; 94(6): 96–104.


Shabaldina E.V., Ryazantsev S.V., Shabaldin A.V. [Miramistin effectiveness in infants and preschool children with tonsils pharyngeal lymphoid ring hypertrophy, with recurrent acute respiratory infections and sensitization for streptococcus pyogenes]. Pediatria. Journal namet after G.N. Speransky 2015; 94(6): 96–104. (In Russ.).


15. Николаева И.В., Герасимова Е.С., Павлова Т.Ю. Эффектив­ность мирамистина в коррекции нарушений микробиоценоза ротоглотки у часто болеющих детей. Российский педиатрический журнал 2016; 19(1): 9–14. DOI 10.18821/1560-9561-2016-19 (1)-9-14


Nikolaeva I.V., Gerasimova E. S., Pavlova T.Yu. [Efficacy of Miramistin in the correction of the oropharynx microbiocenosis in sickly children]. Russian Pediatric Journal 2016; 19(1): 9–14. (In Russ.). DOI 10.18821/1560-9561-2016-19(1)-9-14


16. Зырянов С.К., Байбулатова Е.А. Клинико-фармаколо­гический анализ применения антисептических препаратов в практической медицине. Вопросы практической педиатрии 2021; 16(6): 77–92. DOI: 10.20953/1817-7646-2021-6-77-92


Zyryanov S.K., Baybulatova E.A. [Clinical and pharmacological analysis of antiseptics used in practical medicine]. Clinical Practice in Pediatrics. 2021; 16(6): 77–92 (In Russian). DOI: 10.20953/1817-7646-2021-6-77-92


17. Винцерская Г.А., Притуло О.А., Шеренговская Ю.В., Бабанин В.А., Мараках Марван Якин Нажи. Мирамистин: от дерматовенерологии до профилактики коронавирусной инфекции. Обзор литературы. Российский журнал кожных и венерических болезней 2020; 23(5): 341–6. DOI: https://doi.org/ 10.17816/dv59976


Vintserskaya GA, Pritulo OA, Sherengovskaya YuV, Babanin VA, Marakah M.Ya.N. [Miramistin: from dermatovenerology to prevention of coronavirus infection. Literature review]. Russian Journal of Skin and Venereal Diseases 2020; 23(5): 341–6. (In Russ.). DOI: https://doi.org/10.17816/dv59976


18. Грачева А.В., Корчевая Е.Р., Кудряшова А.М., Борисова О.В., Петруша О.А., Смирнова Д.И. и др. Адаптация МТТ-теста для определения нейтрализующих антител к вирусу SARS-CoV-2. Журнал микробиологии, эпидемиологии и иммунобиологии 2021; 98(3): 253–65. https://doi.org/10.36233/0372-9311-136


Gracheva A.V., Korchevaya E.R., Kudryashova A.M., Borisova O.V., Petrusha O.A., Smirnova D.I. et al. [Adaptation of the MTT assay for detection of neutralizing antibodies against the SARS-CoV-2 virus]. Journal of microbiology, epidemiology and immunobiology 2021; 98(3): 253–65. (In Russ.). DOI: https://doi.org/10.36233/0372-9311-136


19. Ramakrishnan M.A. Determination of 50% endpoint titer using a simple formula. World J. Virol. 2016; 5(2): 85–6. https://doi.org/10.5501/wjv.v5.i2.85


20. Gracheva A.V., Korchevaya E.R., Ammour Y.I., Smirnova D.I., Sokolova O.S., Glukhov G.S. et al. Immunogenic properties of SARS-CoV-2 inactivated by ultraviolet light. Arch. Virol. 2022: 1–11. doi: 10.1007/s00705-022-05530-7


21. Профилактика, диагностика и лечение новой коронавирусной инфекции (COVID-19). Временные методические рекомендации. Версия 16 (18.08.2022). https://edu-rosminzdrav.ru.com/profilaktika-diagnostika-i-lechenie-covid-19/?ysclid=l99yqp3rvz289472438


[Prevention, diagnosis and treatment of a new coronavirus infection (COVID-19). Temporary guidelines. Version 16 (08.18.2022)].https://edu-rosminzdrav.ru.com/profilaktika-diagnostika-i-lechenie-covid-19/?ysclid=l99yqp3rvz 289472438


22. Rawson T.M., Moore L.S.P., Zhu N., Ranganathan N., Skolimowska K., Gilchrist M. et al. Bacterial and Fungal Coinfection in Individuals With Coronavirus: A Rapid Review To Support COVID-19 Antimicrobial Prescribing. Clin. Infect. Dis. 2020; 71(9): 2459–68. doi: 10.1093/cid/ciaa530


About the Autors


Irina A. Leneva, BiolD, Head, Laboratory of Experimental Virology, I.I. Mechnikov Research Institute of Vaccines and Sera, Moscow, Russia; wnyfd385@yandex.ru; https://orcid.org/0000-0002-7755-2714
Anastasia V. Gracheva, Junior Researcher, Laboratory of Molecular Virology, I.I. Mechnikov Research Institute of Vaccines and Sera, Moscow, Russia; anastasiia.gracheva. 95@mail.ru; https://orcid.org/0000-0001-8428-4482
Ekaterina R. Korchevaya, Junior Researcher, Laboratory of Molecular Virology, I.I. Mechnikov Research Institute of Vaccines and Sera, Moscow, Russia; c.korchevaya@gmail.com; https://orcid.org/0000-0002-6417-3301
Daria I. Smirnova, Junior Researcher, Laboratory of Molecular Virology, I.I. Mechnikov Research Institute of Vaccines and Sera, Moscow, Russia; daria.sm.1995@mail.ru; https://orcid.org/0000-0001-7325-0834
Evgeny B. Faizuloev, Cand. Biol. Sci., Head, Laboratory of Molecular Virology, I.I. Mechnikov Research Institute of Vaccines and Sera, Moscow, Russia; faizuloev@mail.ru; https://orcid.org/0000-0001-7385-5083

Вклад авторов. Ленева И.А. – дизайн и проведение исследования, статистическая обработка данных, написание статьи; Грачева А.В. – дизайн и проведение исследования, написание статьи; Корчевая Е.Р. – проведение исследования, статистическая обработка результатов; Смирнова Д.И. – проведение исследования; Файзулоев Е.Б. – дизайн и проведение исследования, редактирование статьи.
Authors contributions. Leneva I.A. – design and conduction of the investigation; statistical processing of the results; writing the article; Gracheva A.V. – design and conduction of the investigation; Korchevaya E.R. – conduction of the investigation; statistical processing of the results; Smirnova D.I. – conduction of the investigation; Fayzuloev E.B. – design and conduction of the investigation; editing the text.


Similar Articles


Бионика Медиа