Proteflazid® vs COVID-19: successes in research

October 29, 2021
1014
Resume

The original antiviral drug Proteflazid® has been used in clinical practice since the early 2000s for the etiotropic treatment of acute respiratory viral diseases due to its ability to block of RNA- and DNA-polymerases viruses. Given that at the beginning of the global pandemic COVID-19 caused by RNA-containing virus of the species SARS-CoV-2 in 2020, the ability of the active substance of the drug to inhibit the activity of 3CL-protease coronavirus SARS-CoV-2 and subsequently confirm the property of the active substance to block the replication of SARS-CoV-2 virus in cell cultures in vitro, it has been extremely important to test the effectiveness of the drug Proteflazid®, drops, for the prevention and treatment of COVID-19 in «off label use». In retrospective clinical studies, it has been shown that Proteflazid® in the conditions of the COVID-19 pandemic contributes to a 2.2-fold reduction in the proportion of sick medical staff, reduction in the proportion of patients with severe disease by 3.3 times, reduction of the average duration of treatment by 1.8 times and the most important is that there is no mortality among the sick medical staff and patients who has administered the drug.

References

  • 1. Grynevych O.Y., Markovich I.G. (2013) Coronavirus: problems and prospects. UMJ, 3: 45–48.
  • 2. Grynevych O., Borshov S., Matyash V. et al. (2021) Proteflazid® effectiveness for prevention and treatment of acute viral respiratory infections in the conditions of COVID-19 in the conditions of SARS-COV-2. Pol. Med. J., XLIX (292): 255–265.
  • 3. Matyash V., Grynevych O., Broun T. (2019) PROTEFLAZID®: clinical studies as evidence base of its antiviral activity. Pol. Med. J., XLVI (271): 30–31.
  • 4. Instruction for medical use of the drug Proteflazid® (as amended, in accordance with the order of the Ministry of Health of Ukraine dated 06.08.2021 № 1680).
  • 5. Palchikovska L.G., Vasilchenko O.V., Platonov M.O. et al. (2013) Antiviral properties of plant flavonoids — inhibitors of DNA and RNA synthesis. Biopolymers and Cell, 29 (2): 150–156.
  • 6. Rybalko S.L. (2020) Study of the antiviral activity of the drug Proteflazid®, its active structures in the model of coronavirus transmissible gastroenteritis of pigs. SI «L.V. Gromashevsky Institute of Epidemiology and Infectious Diseases of the NAMS of Ukraine», 42 p.
  • 7. Rybalko S.L. (2010) Report on the study of the mechanisms of action of biologically active substances of the therapeutic substance Proteflazid. SI «L.V. Gromashevsky Institute of Epidemiology and Infectious Diseases of the NAMS of Ukraine», Kyiv, 83 p.
  • 8. Abian O., Ortega-Alarcon D., Jimenez-Alesanco A. et al. (2020) Structural stability of SARS-CoV-2 3CLpro and identification of quercetin as an inhibitor by experimental screening. Int. J. Biol. Macromol., 164: 1693–1703.
  • 9. Deryabin O.N., Zavelevich M.P., Starosila D.B. et al. (2020) Natural polyphenols as inhibitors of the interaction of coronaviruses with cells: a review of the literature and experimental data. UMJ, 3 (137), Vol. 1: 1–5.
  • 10. Chen S., Short J.A., Young D.F. et al. (2010) Heterocellular induction of interferon by negative-sense RNA viruses. Virology, 407: 247–255.
  • 11. Jo S., Kim S., Shin D.H., Kim M.S. (2020) Inhibition of SARS-CoV 3CL protease by flavonoids. J. Enzyme Inhib. Med. Chem., 35(1): 145–151.
  • 12. Lee C. (2018) Therapeutic Modulation of Virus-Induced Oxidative Stress via the Nrf2-Dependent Antioxidative Pathway. Oxidative Med. Cell. Longev., 6208067.
  • 13. Li F. (2012) Evidence for a common evolutionary origin of coronavirus spike protein receptor-binding subunits. J. Virol., 86: 2856–2858.
  • 14. Li W., Moore M.J., Vasilieva N. et al. (2003) Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature, 426: 450–454.
  • 15. McCord J.M., Hybertson B.M., Cota-Gomez A., Gao B. (2020) Nrf2 Activator PB125® as a Potential Therapeutic Agent Against COVID-19. bioRxiv 2020.
  • 16. Nguyen T.T., Woo H.J., Kang H.K. et al. (2012) Flavonoid-mediated inhibition of SARS coronavirus 3C-like protease expressed in Pichia pastoris. Biotechnol. Lett., 34: 831–838.
  • 17. Mendonca P., Soliman K.F.A. (2020) Flavonoids Activation of the Transcription Factor Nrf2 as a Hypothesis Approach for the Prevention and Modulation of SARS-CoV-2 Infection Severity. Antioxidants (Basel), 9: 659. doi:10.3390/antiox9080659.
  • 18. Ryu Y.B., Jeong H.J., Kim J.H. et al. (2010) Biflavonoids from Torreya nucifera displaying SARS-CoV 3CL(pro) inhibition. Bioorg. Med. Chem., 18: 7940–7947.
  • 19. Seelinger G., Merfort I., Schempp C.M. (2008) Anti-oxidant, antiinflammatory and anti-allergic activities of luteolin. Planta Med., 74(14): 1667–1677.
  • 20. Silva-Palacios A., Ostolga-Chavarria M., Zazueta C., Konigsberg M. (2018) Nrf2: Molecular and epigenetic regulation during aging. Ageing Res. Rev., 47: 31–40.
  • 21. Theoharides T.C. (2020) COVID-19, pulmonary mast cells, cytokine storms and beneficial actions of luteolin. BioFactors: 1–3.
  • 22. Wang M.M., Lu M., Zhang C.L. et al. (2018) Oxidative stress modulates the expression of toll-like receptor 3 during respiratory syncytial virus infection in human lung epithelial A549 cells. Mol. Med. Rep., 18: 1867–1877.
  • 23. Weng Z., Patel A.B., Panagiotidou S., Theoharides T.C. (2015) The novel flavone tetramethoxyluteolin is a potent inhibitor of human mast cells. J. Allergy Clin. Immunol., 135(4):1044–1052.e5.
  • 24. Wrapp D., Wang N., Corbett K.S. et al. (2020) structure of the 2019-nCoV spike in the prefusion conformation. Science, 367: 1260–1263.
  • 25. Xue G., Gong L., Yuan C. et al. (2017) A structural mechanism of flavonoids in inhibiting serine proteases. Food Funct., 8(7): 2437–2443.
  • 26. Zakaryan H., Arabyan E., Oo A., Zandi K. (2017) Flavonoids: Promising natural compounds against viral infections. Arch. Virol., 162: 2539–2551.
  • 27. Luzhetskyy A. (2021) Report: Inhibition of 3CL protease (SARS-CoV-2) by proteflasid. Helmholtz Centre for Infection Research. University of Saarland, Germany. Saarbrucken, 2 р.
  • 28. Tseng Ch.-T.K., Drelich A.K. (2021) Report «The efficacy assessment of new compound against SARS-CoV-2 infection in in vitro models. Galveston National Laboratory, Galveston, USA, 4 р.
  • 29. SI «L.V. Gromashevsky Institute of Epidemiology and Infectious Diseases of the NAMS of Ukraine», Institute of Molecular Biology and Genetics of the NAMS of Ukraine, UKRMEDPATENTINFORM (2021) Information letter on innovations in the field of health care «Antiviral activity of the flavonoid drug Proteflazid®», 4 p.
  • 30. Instruction for medical use of the drug Flavovir® (as amended, in accordance with the order of the Ministry of Health of Ukraine dated 10.09.2021 № 1922).
  • 31. Momotyuk L.E., Yashchenko L.O., Motuzka O.M. (2020) Final report «Formation of the database and statistical analysis of the effectiveness of the drug Proteflazid, drops in the conditions of COVID-19». National Academy of Statistics, Accounting and Auditing. Kyiv, 38 p.
  • 32. Recommendation letter of the NAMS of Ukraine dated 16.03.2021 № 5-03/487 on the expediency of using the drug Proteflazid®, drops, in COVID-19.
  • 33. Karamuska T. (2020) Interim report «Evaluation of the antiviral activity of a test item against SARS-CoV-2 in vitro in Vero E6 cells» IRTA-CreSA Universitat Autonoma de Barcelona, Barcelona, Spain, 8 р.