In vitro antiviral activity of VIFERON® rectal suppositories against SARS-CoV-2

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Abstract

In 2020–2021, the world was engulfed by the pandemic of a new coronavirus infection (COVID-19) caused by the SARS-CoV-2 virus. The low population coverage with vaccination against COVID-19 and the lack of herd immunity result in the need to find an effective and safe etiotropic treatment. Medicinal agents for treatment of COVID-19, approved while preparing this publication, have several limitations related to the conditions of their use and/or population category. In this situation, interferon-containing drugs widely used in Russia and the CIS for prevention and treatment of viral infectious diseases, i.e. ARVI and influenza, may hold promise. This study aims to confirm in vitro antiviral activity against SARS-CoV-2 for the preparation VIFERON® containing recombinant human interferon alpha-2b (IFNα-2b). Materials and methods. Vero CCL-81 cells were infected with hCoV-19/StPetersburg-RII3524VR4/2020 strain of SARS-CoV-2 at doses of 10 TCID50 or 100 TCID50 per well. The suppressive effect of IFN-2b, extracted from VIFERON® in dosage form of rectal suppositories, was evaluated by qRT-PCR at 24 h and 48 h after the infection of cells in two schemes, simulating preventive (24 h before infection) and therapeutic (2 h after infection) use of drugs. Results. IFNα-2b at concentrations of 800, 400, 200, 100 and 50 IU/ml, extracted from rectal suppositories of VIFERON®, showed high biological activity, displayed as inhibition of SARS-CoV-2 strain replication in both infectious doses evaluated either at 24 h or at 48 h after cell infection. The “preventive” vs. “therapeutic” scheme was found to be more effective. In the “preventive” scheme the virus titre decreased by more than 3 lg TCID50 at 24 hours post-infection and by 5–6 lg TCID50 at 48 hours post-infection after administration of 800 IU/ml IFNα-2b. Conclusion. The study results evidence that VIFERON® in dosage form of rectal suppositories may be promising for prevention and treatment of new coronavirus infection in clinical practice.

About the authors

I. N. Isakova-Sivak

Institute of Experimental Medicine

Email: isakova.sivak@iemspb.ru
ORCID iD: 0000-0002-2801-1508

Irina N. Isakova-Sivak - PhD, MD (Biology), Head of the Laboratory of Immunology and Prevention of Viral Infections, A.A. Smorodintsev Department of Virology, Institute of Experimental Medicine.

St. Petersburg.

Россия

E. A. Stepanova

Institute of Experimental Medicine

Email: fedorova.iem@gmail.com
ORCID iD: 0000-0002-8670-8645

Ekaterina A. Stepanova - PhD (Biology), Senior Researcher, A.A. Smorodintsev Department of Virology, Institute of Experimental Medicine.

St. Petersburg.

Россия

L. G. Rudenko

Institute of Experimental Medicine

Email: rudenko.lg@iemspb.ru
ORCID iD: 0000-0002-0107-9959

Larisa G. Rudenko - PhD, MD (Medicine), Professor, Head of A.A. Smorodintsev Department of Virology, Institute of Experimental Medicine.

St. Petersburg.

Россия

M. S. Bartov

N.F. Gamaleya Federal Research Center for Epidemiology and Microbiology

Author for correspondence.
Email: mike.bartov@gmail.com
ORCID iD: 0000-0002-3610-2119

Michael S. Bartov - PhD (Biology), Researcher, Laboratory of Biologically Active Nanostructures, N.F. Gamaleya Federal Research Center for Epidemiology and Microbiology.

123098, Moscow, Gamaleya str., 18.

Phone: +7 910 002-29-52.

Россия

E. N. Vyzhlova

N.F. Gamaleya Federal Research Center for Epidemiology and Microbiology

Email: evizhlova@yandex.ru
ORCID iD: 0000-0003-3054-8694

Eugenia N. Vyzhlova - PhD (Biology), Researcher, Laboratory of Ontogenesis and Interferon System Remediation, N.F. Gamaleya Federal Research Center for Epidemiology and Microbiology.

Moscow.

Россия

V. V. Malinovskaya

N.F. Gamaleya Federal Research Center for Epidemiology and Microbiology

Email: malinovskaya@gamaleya.org
ORCID iD: 0000-0003-1856-8924

Valentina V. Malinovskaya - PhD, MD (Biology), Professor, Head of the Laboratory of Ontogenesis and Interferon System Remediation, N.F. Gamaleya Federal Research Center for Epidemiology and Microbiology.

Moscow.

Россия

References

  1. Понежева Ж.Б., Гришаева А.А., Маннанова И.В., Купченко А.Н., Яцышина С.Б., Краснова С.В., Малиновская В.В., Акимкин В.Г. Профилактическая эффективность рекомбинантного интерферона α-2b в условиях пандемии COVID-19 // Лечащий врач. 2020. Т. 12, № 23. С. 56–60. doi: 10.26295/OS.2020.29.66.011
  2. Audi A., AlIbrahim M., Kaddoura M., Hijazi G., Yassine H.M., Zaraket H. Seasonality of respiratory viral infections: will COVID-19 follow suit? Front. Public Health, 2020, vol. 8: 567184. doi: 10.3389/fpubh.2020.567184
  3. Beilharz M.W., Cummins M.J., Bennett A.L., Cummins J.M. Oromucosal administration of interferon to humans. Pharmaceuticals (Basel), 2010, vol. 3, no. 2, pp. 323–344. doi: 10.3390/ph3020323
  4. Burki T.K. Challenges in the rollout of COVID-19 vaccines worldwide. Lancet Respir. Med., 2021, vol. 9, no. 4, pp. e42–e43. doi: 10.1016/S2213-2600(21)00129-6
  5. Cinatl J., Morgenstern B., Bauer G., Chandra P., Rabenau H., Doerr H.W. Treatment of SARS with human interferons. Lancet, 2003, vol. 362, no. 9380, pp. 293–294. doi: 10.1016/s0140-6736(03)13973-6
  6. Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat. Microbiol., 2020, vol. 5, no. 4, pp. 536–544. doi: 10.1038/s41564-020-0695-z
  7. COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU). URL: https://coronavirus.jhu.edu/map.html
  8. Desmyter J., Melnick J.L., Rawls W.E. Defectiveness of interferon production and of rubella virus interference in a line of african green monkey kidney cells (Vero). J. Virol., 1968, vol. 2, no. 10, pp. 955–961. doi: 10.1128/JVI.2.10.955-961.1968
  9. Felgenhauer U., Schoen A., Gad H.H., Hartmann R., Schaubmar A.R., Failing K., Drosten C., Weber F. Inhibition of SARS-CoV-2 by type I and type III interferons. J. Biol. Chem., 2020, vol. 295, no. 41, pp. 13958–13964. doi: 10.1074/jbc.AC120.013788
  10. Gao L., Yu S., Chen Q., Duan Z., Zhou J., Mao C., Yu D., Zhu W., Nie J., Hou Y. A randomized controlled trial of low-dose recombinant human interferons alpha-2b nasal spray to prevent acute viral respiratory infections in military recruits. Vaccine, 2010, vol. 28, no. 28, pp. 4445–4451. doi: 10.1016/j.vaccine.2010.03.062
  11. Graichen H. What is the difference between the first and the second/third wave of COVID-19? — German perspective. J. Orthop., 2021, vol. 24, pp. A1–A3. doi: 10.1016/j.jor.2021.01.011
  12. Ianevski A., Yao R., Zusinaite E., Lello L.S., Wang S., Jo E., Yang J., Lysvand H., Løseth K., Oksenych V., Tenson T., Windisch M.P., Poranen M., Nieminen A.I., Nordbø S.A., Fenstad M.H., Grødeland G., Aukrust P., Trøseid M., Kantele A., Merits A., Bjørås M., Kainov D.E. Synergistic interferon alpha-based drug combinations inhibit SARS-CoV-2 and other viral infections in vitro. bioRxiv, 2021: 2021.01.05.425331.
  13. Karako K., Song P., Chen Y., Tang W., Kokudo N. Overview of the characteristics of and responses to the three waves of COVID-19 in Japan during 2020–2021. Biosci. Trends, 2021, vol. 15, no. 1, pp. 1–8. doi: 10.5582/bst.2021.01019
  14. Lokugamage K.G., Hage A., de Vries M., Valero-Jimenez A.M., Schindewolf C., Dittmann M., Rajsbaum R., Menachery V.D. Type I interferon susceptibility distinguishes SARS-CoV-2 from SARS-CoV. J. Virol., 2020, vol. 94, no. 23: e01410-20.
  15. Mantlo E., Bukreyeva N., Maruyama J., Paessler S., Huang C. Antiviral activities of type I interferons to SARS-CoV-2 infection. Antiviral. Res., 2020, vol. 179: 104811. doi: 10.1016/j.antiviral.2020.104811
  16. Sallard E., Lescure F.X., Yazdanpanah Y., Mentre F., Peiffer-Smadja N. Type 1 interferons as a potential treatment against COVID-19. Antiviral. Res., 2020, vol. 178: 104791. doi: 10.1016/j.antiviral.2020.104791
  17. Seong H., Hyun H.J., Yun J.G., Noh J.Y., Cheong H.J., Kim W.J., Song J.Y. Comparison of the second and third waves of the COVID-19 pandemic in South Korea: importance of early public health intervention. Int. J. Infect. Dis., 2021, vol. 104, pp. 742– 745. doi: 10.1016/j.ijid.2021.02.004
  18. Stockman L.J., Bellamy R., Garner P. SARS: systematic review of treatment effects. PLoS Med., 2006, vol. 3, no. 9: e343. doi: 10.1371/journal.pmed.0030343
  19. Wang M., Cao R., Zhang L., Yang X., Liu J., Xu M., Shi Z., Hu Z., Zhong W., Xiao G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res., 2020, vol. 30, no. 3, pp. 269–271. doi: 10.1038/s41422-020-0282-0
  20. WHO. Coronavirus disease 2019 (COVID-19): situation report, 51. WHO, 2020. 9 p.
  21. WHO. Novel Coronavirus (2019-nCoV): situation report, 22. WHO, 2020. 7 p.

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Copyright (c) 2022 Isakova-Sivak I.N., Stepanova E.A., Rudenko L.G., Bartov M.S., Vyzhlova E.N., Malinovskaya V.V.

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