Assessment of the antiviral activity of 2HCl*H-His-Rim compound compared to the anti-influenza drug Arbidol for influenza caused by A/duck/Novosibirsk/56/05 (H5N1) (Influenza A virus, Alphainfluenzavirus, Orthomyxoviridae)

Cover Page


Cite item

Full Text

Abstract

Introduction. The emergence of influenza virus strains with drug resistance to antiviral drugs requires finding new compounds, potential direct-acting inhibitors. Аdamantane compounds drugs used since the 1960s have lost their activity the resulting due to resistance. Only neuraminidase inhibitors such as zanamivir and oseltamivir have been approved by WHO for influenza treatment. The Russian pharmaceutical drug Arbidol (Umifenovirum) is actively used in Russia. This drug is used to treat influenza in Russia, China and most post-Soviet republics. This work presents a new derivative of aminoadamantane - dichlorohydrate L-histidyl-1-adamantayl ethylamine (2HCl*H-His-Rim), which showed a high level of inhibition of strains of influenza virus A in vitro.
Objectives. Comparison of antiviral properties of the new synthetic low-molecular inhibitor of influenza A virus replication and Arbidol drug pharmacy.
Methods. The compound 2HCl*H-His-Rim was obtained by classical peptide synthesis methods. It was identified by methods of mass spectrometry, infrared spectroscopy (IR) and nuclear magnetic resonance spectroscopy (NMR). Its antiviral properties have been studied in vitro for monolayer of cells Vero-E6 infected with a high-virulent strain of A/duck/Novosibirsk/56/06 (H5N1) influenza virus at various injection schemes of the investigated compounds.
The results. The antiviral activity of the 2HCl*H-His-Rim compound against the highly pathogenic strain of the influenza A/H5N1 virus was slightly higher than for the known pharmacy drug arbidol.
Discussion. The difference in antiviral activity of these two compounds is explained by different mechanisms of action on the viral particle.
Conclusion. The 2HCl*H-His-Rim compound can be recommended as a candidate for preclinical and clinical trials in order to obtain an etiotropic antiviral drug based on it, due to its high efficacy and economic and synthetic availability. The synthetic compound 2HCl*H-His-Rim acts on influenza A virus variants resistant to Rimantadine and Amantadine.

About the authors

P. G. Deryabin

National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya

Email: fake@neicon.ru
ORCID iD: 0000-0002-8522-9554
Moscow, 123098 Russian Federation

T. M. Garaev

National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya

Author for correspondence.
Email: tmgaraev@gmail.com
ORCID iD: 0000-0002-3651-5730

PhD., Lead Researcher of the laboratory of molecular diagnostics 

Moscow, 123098

Russian Federation

M. P. Finogenova

National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya

Email: fake@neicon.ru
ORCID iD: 0000-0002-3611-3897
Moscow, 123098 Russian Federation

A. I. Odnovorov

Russian Peoples’ Friendship University of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0001-9355-2522
Moscow, 117198 Russian Federation

References

  1. Stouffer A.L., Acharya R., Salom D., Levine A.S., Di Costanzo L., Soto C.S., et al. Structural basis for the function and inhibition of an influenza virus proton channel. Nature. 2008; 451(7178): 596-9. DOI: https://doi.org/10.1038/nature06528
  2. Duong-Ly K.C., Nanda V., Degrado W.F., Howard K.P. The conformation of the pore region of the M2 proton channel depends on lipid bilayer environment. Protein Sci. 2005; 14(4): 856-61. DOI: https://doi.org/10.1110/ps.041185805
  3. Bright R.A., Medina M.J., Xu X., Perez-Oronoz G., Wallis T.R., Davis X.M., et al. Incidence of adamantane resistance among influenza A (H3N2) viruses isolated worldwide from 1994 to 2005: a cause for concern. Lancet. 2005; 366(9492): 1175-81. DOI: https://doi.org/10.1016/S0140-6736(05)67338-2
  4. Wang C., Takeuchi K., Pinto L.H., Lamb R.A. Ion channel activity of influenza A virus M2 protein: characterization of the amantadine block. J. Virol. 1993; 67(9): 5585-94.
  5. WHO Guidelines for Pharmacological Management of Pandemic Influenza A(H1N1) 2009 and other Influenza Viruses: Part I. Geneva: WHO; 2010.
  6. Centers for Disease Control and Prevention Recommendations: CS HCVG-15-FLU-107; 2018.
  7. Boriskin Y., Leneva I., Pécheur E.I., Polyak S.J. Arbidol: a broadspectrum antiviral compound that bloks viral fusion. Curr. Med. Chem. 2008; 15(10): 997-1005. DOI: https://doi.org/10.2174/092986708784049658
  8. Leneva I.A., Russell R.J., Boriskin Y.S., Hay A.J. Characteristics of arbidol-resistant mutants of influenza virus: implications for the mechanism of anti-influenza action of arbidol. Antiviral Res. 2009; 81(2): 132-40. DOI: https://doi.org/10.1016/j.antiviral.2008.10.009
  9. Nasser Z.H., Swaminathan K., Müller P., Downard K.M. Inhibition of influenza hemagglutinin with the antiviral inhibitor arbidol using a proteomics based approach and mass spectrometry. Antiviral Res. 2013; 100(2): 399-406. DOI: https://doi.org/10.1016/j.antiviral.2013.08.021
  10. Вrancato V., Peduto A., Wharton S., Martin S., More V., Di Mola A., et al. Design of inhibitors of influenza virus membrane fusion: synthesis, structure-activity relationship and in vitro antiviral activity of a novel indole series. Antiviral Res. 2013; 99(2): 125-35. DOI: https://doi.org/10.1016/j.antiviral.2013.05.005
  11. Дерябин П.Г., Гараев Т.М., Финогенова М.П., Ботиков А.Г., Шибнев В.А. Аминокислотные производные адамантанового кабоцикла способны ингибировать репликацию высоковирулентного вируса птичьего гриппа A/H5N1. Бюллетень экспериментальной биологии и медицины. 2014; 157(1): 73-6.
  12. Прилипов А.Г., Львов Д.К., Щелканов М.Ю., Алипер Т.И., Дерябин П.Г., Непоклонов Е.А. и др. Метод первичной изоляции штаммов вируса гриппа А, штамм virus A/duck/Novosibirsk/56/05 H5N1 для приготовления диагностических,
  13. профилактических и лечебных препаратов, для оценки противовирусной активности различных соединений. Патент РФ 2309983; 2005.
  14. Haviernik J., Štefánik M., Fojtíková M., Kali S., Tordo N., Rudolf I., et al. Arbidol (Umifenovir): A Broad-Spectrum Antiviral Drug That Inhibits Medically Important Arthropod-Borne Flaviviruses. Viruses. 2018; 10(4): E184. DOI: https://doi.org/10.3390/v10040184
  15. Шибнев В.А., Гараев Т.М., Финогенова М.П., Шевченко Е.С., Бурцева Е.И. Некоторые пути преодоления резистентности вирусов гриппа А к препаратам адамантанового ряда. Химикофармацевтический журнал. 2012; 46(1): 36-40.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2019 Deryabin P.G., Garaev T.M., Finogenova M.P., Odnovorov A.I.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС77-77676 от 29.01.2020.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies