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In vitro antiviral activity of a double-stranded RNA sodium salt-based medicinal product against SARS-CoV-2

https://doi.org/10.30895/2221-996X-2023-23-3-290-299

Abstract

Scientific relevance. Innate immune activation in the early phases of COVID-19 infection and subsequent interferon induction may help control viral replication and protect cells not yet infected with SARS-CoV-2. Thus, immunostimulants that induce interferon (IFN), including double-stranded RNA-based agents, are a promising means of post-exposure prophylaxis and treatment of COVID-19 at early stages.

Aim. The study evaluated the in vitro antiviral activity of a double-stranded RNA sodium salt-based medicinal product against SARS-CoV-2.

Materials and methods. The authors analysed the double-stranded RNA sodium salt-based medicinal product RADAMIN®VIRO using Vero cells and the Delta variant of SARS-CoV-2 (B.1.617). The virus titre was calculated as the tissue cytopathic dose that caused 50% cell death. The authors measured the content of IFN-α and IFN-γ in the culture fluid by enzyme immunoassay and assessed the viral load by real-time polymerase chain reaction (using the cycle threshold value) and by titration (using Vero cells).

Results. The studied double-stranded RNA sodium salt-based medicinal product at a concentration of 250 or 500 μg/mL induced IFN-α and IFN-γ expression by Vero cells, thus increasing their resistance to SARS-CoV-2. The authors evaluated the antiviral activity of the medicinal product based on the virus titre, viral load, and cell monolayer damage. The antiviral activity became clear 24 h after treatment, which confirmed the ability of the medicinal product to inhibit the replication of the SARS-CoV-2 virus in vitro as early as the first day after infection.

Conclusions. The double-stranded RNA sodium salt-based medicinal product induced IFN-α and IFN-γ synthesis in Vero cells, increasing their resistance to SARS-CoV-2 infection in vitro. These results demonstrate the immunomodulatory and antiviral potential of the medicinal product.

About the Authors

G. M. Ignatyev
I. Mechnikov Research Institute for Vaccines and Sera
Russian Federation

Georgy M. Ignatyev, Dr. Sci. (Med.), Professor

5A Maly Kazenny Ln., Moscow 105064



E. Yu. Shustova
Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis)
Russian Federation

Elena Yu. Shustova

8/1 Village of the Institute of Poliomyelitis, Moskovsky settlement, Moscow 108819

 



E. A. Rogozhina
MIREA—Russian Technological University
Russian Federation

Ekaterina A. Rogozhina

78 Vernadsky Ave, Moscow 119454



P. A. Belyi
A.I. Yevdokimov Moscow State University of Medicine and Dentistry
Russian Federation

Peter A. Belyi, Cand. Sci. (Med.)

20/1 Delegatskaya St., Moscow 127473



K. Ya. Zaslavskaya
National Research Ogarev Mordovia State University
Russian Federation

Kira Ya. Zaslavskaya

68 Bolshevistskaya St., Saransk 430005, Republic of Mordovia



V. A. Merkulov
Scientific Centre for Expert Evaluation of Medicinal Products
Russian Federation

Vadim A. Merkulov, Dr. Sci. (Med.), Professor

8/2 Petrovsky Blvd, Moscow 127051



References

1. Cucinotta D, Vanelli M. WHO declares COVID-19 a pandemic. Acta Biomed. 2020;91(1):157–60. https://doi.org/10.23750/abm.v91i1.9397

2. Seyedpour S, Khodaei B, Loghman AH, Seyedpour N, Kisomi MF, Balibegloo M, et al. Targeted therapy strategies against SARS‐CoV‐2, cell entry mechanisms: A systematic review of in vitro and in vivo studies. J Cell Physiol. 2020;236(4):2364–92. https://doi.org/10.1002/jcp.30032

3. Bolevich SB, Bolevich SS. Complex mechanism of COVID-19 development. Sechenov Medical Journal. 2020;11(2):50–61 https://doi.org/10.47093/2218-7332.2020.11.2.50-61

4. Andreev-Andrievskiy AA, Zinovkin RA, Mashkin MA, Frolova OY, Kazaishvili YG, Scherbakova VS, et al. Gene expression pattern of Peyer’s patch lymphocytes exposed to kagocel suggests pattern-recognition receptors mediate its action. Front Pharmacol. 2021;12:679511. https://doi.org/10.3389/fphar.2021.679511

5. Gu W, Gan H, Ma Y, Xu L, Cheng J, Li B, et al. The molecular mechanism of SARS-CoV-2 evading host antiviral innate immunity. Virol J. 2022;19(1):49. https://doi.org/10.1186/s12985-022-01783-5

6. Kostinov MP, Markelova EV, Svitich OA, Polishchuk VB Immunological methods of SARS-CoV-2 and potential drugs for the prevention and treatment of COVID-19. Pulmonology. 2020;30(5):700–8. https://doi.org/10.18093/0869-0189-2020-30-5-700-708

7. Barnard DL, Day CW, Bailey K, Heiner M, Montgomery R, Lauridsen L, et al. Evaluation of immunomodulators, interferons and known in vitro SARS-CoV inhibitors for inhibition of SARS-CoV replication in BALB/c mice. Antivir Chem Chemother. 2006;17(5):275–84. https://doi.org/10.1177/095632020601700505

8. Day CW, Baric R, Cai SX, Frieman M, Kumaki Y, Morrey JD, et al. A new mouse-adapted strain of SARS-CoV as a lethal model for evaluating antiviral agents in vitro and in vivo. Virology. 2009;395(2):210–22. https://doi.org/10.1016/j.virol.2009.09.023

9. Overton ET, Goepfert PA, Cunningham P, Carter WA, Horvath J, Young D, Strayer DR. Intranasal seasonal influenza vaccine and a TLR-3 agonist, rintatolimod, induced cross-reactive IgA antibody formation against avian H5N1 and H7N9 influenza HA in humans. Vaccine. 2014;32(42):5490–5. https://doi.org/10.1016/j.vaccine.2014.07.078

10. Kozlowski A, Charles SA, Harris JM. Development of pegylated interferons for the treatment of chronic hepatitis C. BioDrugs. 2001;15(7):419–29. https://doi.org/10.2165/00063030-200115070-00001

11. Nicodemus CF, Berek JS. TLR3 agonists as immunotherapeutic agents. Immunotherapy. 2010;2(2):137–40. https://doi.org/10.2217/imt.10.8

12. Mustafa DAM, Saida L, Latifi D, Wismans LV, de Koning W, Zeneyedpour L. Rintatolimod induces antiviral activities in human pancreatic cancer cells: opening for an Anti-COVID-19 opportunity in cancer patients. Cancers (Basel). 2021;13(2):2896. https://doi.org/10.3390/cancers13122896

13. Ershov FI, Kiselev OI. Interferons and their inductors (from molecules to drugs). Moscow: GEOTAR-Media; 2005 (In Russ.).

14. Kozlovskaya L, Piniaeva A, Ignatyev G, Selivanov A, Shishova A, Kovpak A, et al. Isolation and phylogenetic analysis of SARS-CoV-2 variants collected in Russia during the COVID-19 outbreak. Int J Infect Dis. 2020;99:40–6. https://doi.org/10.1016/j.ijid.2020.07.024

15. Ianevski A, Yao R, Zusinaite E, Lello LS, Wang S, Jo E, et al. Synergistic interferon-alpha-based combinations for treatment of SARS-CoV-2 and other viral infections. Viruses. 2021;13(12):2489. https://doi.org/10.3390/v13122489

16. Sallard E, Lescure FX, Yazdanpanah Y, Mentre F, Peiffer-Smadja N. Type 1 interferons as a potential treatment against COVID-19. Antiviral Res. 2020;178:104791. https://doi.org/10.1016/j.antiviral.2020.104791

17. Ribero MS, Jouvenet N, Dreux M, Nisole S. Interplay between SARS-CoV-2 and the type I interferon response. PLoS Pathog. 2020;16(7):e1008737. https://doi.org/10.1371/journal.ppat.1008737

18. Todorović-Raković N, Whitfield JR. Between immunomodulation and immunotolerance: The role of IFNγ in SARS-CoV-2 disease. Cytokine. 2021;146:155637. https://doi.org/10.1016/j.cyto.2021.155637

19. Karber G. Beitragzurkollecktiven behandlungpharmakologischer reihenversuche. Arch Exptl Pathol Pharmakol. 1931;162:480–3.

20. Villinger F, Brar SS, Mayne A, Chikkala N, Ansari AA. Comparative sequence analysis of cytokine genes from human and nonhuman primates. J Immunol. 1995;155:3946–54. https://doi.org/10.4049/jimmunol.155.8.3946

21. Felger JS, Alagbe O, Hu F, Mook D, Freeman AA, Sanchez MM, et al. Effects of interferon-alpha on rhesus monkeys: a non-human primate model of cytokine-induced depression. Biol Psychiatry. 2007;62(11):1324–33. https://doi.org/10.1016%2Fj.biopsych.2007.05.026

22. Willette AA, Lubach GR, Coe CL. Environmental context differentially affects behavioral, leukocyte, cortisol, and interleukin-6 responses to low doses of endotoxin in the rhesus monkey. Brain Behav Immun. 2007;21(6):807–15. https://doi.org/10.1016/j.bbi.2007.01.007


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Ignatyev G.M., Shustova E.Yu., Rogozhina E.A., Belyi P.A., Zaslavskaya K.Ya., Merkulov V.A. In vitro antiviral activity of a double-stranded RNA sodium salt-based medicinal product against SARS-CoV-2. Biological Products. Prevention, Diagnosis, Treatment. 2023;23(3):290-299. (In Russ.) https://doi.org/10.30895/2221-996X-2023-23-3-290-299

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ISSN 2221-996X (Print)
ISSN 2619-1156 (Online)