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)
- 作者: Deryabin P.G.1, Garaev T.M.1, Finogenova M.P.1, Odnovorov A.I.2
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隶属关系:
- National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya
- Russian Peoples’ Friendship University of Russia
- 期: 卷 64, 编号 6 (2019)
- 页面: 268-273
- 栏目: ORIGINAL RESEARCH
- URL: https://ogarev-online.ru/0507-4088/article/view/118012
- DOI: https://doi.org/10.36233/0507-4088-2019-64-6-268-273
- ID: 118012
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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.
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.
作者简介
P. 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 俄罗斯联邦
T. Garaev
National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya
编辑信件的主要联系方式.
Email: tmgaraev@gmail.com
ORCID iD: 0000-0002-3651-5730
PhD., Lead Researcher of the laboratory of molecular diagnostics
Moscow, 123098
M. 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 俄罗斯联邦
A. Odnovorov
Russian Peoples’ Friendship University of Russia
Email: fake@neicon.ru
ORCID iD: 0000-0001-9355-2522
Moscow, 117198 俄罗斯联邦
参考
- 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
- 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
- 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
- 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.
- WHO Guidelines for Pharmacological Management of Pandemic Influenza A(H1N1) 2009 and other Influenza Viruses: Part I. Geneva: WHO; 2010.
- Centers for Disease Control and Prevention Recommendations: CS HCVG-15-FLU-107; 2018.
- 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
- 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
- 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
- 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
- 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.
- 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,
- профилактических и лечебных препаратов, для оценки противовирусной активности различных соединений. Патент РФ 2309983; 2005.
- 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
- 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.
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