Статья

Adamantan derivatives capable of inhibiting the reproduction of a Rimantadine resistant strain of influenza A(H1N1)pdm09 virus (Influenza A virus, Alphainfluenzavirus, Orthomyxoviridae) [Производные адамантана, способные ингибировать репродукцию резистентного к римантадину штамма вируса гриппа А(H1N1)pdm09 (Influenza A virus, Alphainfluenzavirus, Orthomyxoviridae)]

T. Garaev, A. Odnovorov, E. Kirillova, E. Burtseva, M. Finogenova, E. Mukasheva, T. Grebennikova,
2021

Introduction. Adamantanthane-type drugs such as rimantadine and amantadine have long been used to treat diseases caused by influenza A virus. However, as a result of the mutations, influenza viruses have become resistant to aminoadamantans. The target for these drugs was the protein channel M2. Influenza A virus M2 viroporin in the protein shell forms fairly specific ion channels with a diameter of about 11 Å, specializing in transporting protons inside the viral particle (virion). Restoration of the antiviral properties of adamantanthane-type drugs consists in the selection of advanced functional groups bound by the carbocycle to find new sites of binding to the protein target M2. The рurpose of the study is to identify the antiviral properties of new adamantanum derivatives to the pandemic strain of influenza A virus in vitro. Material and methods. Compounds of aminoadamantans with amino acids and other organic molecules were obtained by classical peptide synthesis methods. The structure of the compound was tested by means of physical and chemical methods. Antiviral properties of synthetic compounds were studied in vitro on monolayer MDCK cells infected with pandemic strain of influenza A/California/07/2009 virus in two schemes of administration of investigated compounds and virus. Results. The reference strain of the influenza virus A/California/07/2009(H1N1) was sensitive to the compounds under test in varying degrees. The antiviral activity of the compounds was expressed in a 50% inhibitory concentration (IС50) ranging from 0.5 to 2.5 мкM, which is generally a good indicator for the Rimantadine/Amantadine resistant strain. Discussion. The values of the IС50 for compounds introduced two hours before contact with the virus were slightly higher than those for single-moment introduction of the substance and virus. The effect of increasing the inhibitory concentration in the prophylactic scheme of compounds was valid for all compounds of the experiment. Conclusion. The presented synthetic compounds are active against the variant of influenza A virus resistant to Rimantadine and Amantadine preparations. The obtained compounds can be used as model structures for creation of a new drug of direct action against advanced strains of influenza A virus. © 2020 Izdatel'stvo Meditsina. All rights reserved.

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  • 1. Version of Record от 2021-04-27

Метаданные

Об авторах
  • T. Garaev
    National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya, Moscow, 123098, Russian Federation
  • A. Odnovorov
    Russian Peoples’ Friendship University of Russia, Moscow, 117198, Russian Federation
  • E. Kirillova
  • E. Burtseva
  • M. Finogenova
  • E. Mukasheva
  • T. Grebennikova
Название журнала
  • Voprosy Virusologii
Том
  • 65
Выпуск
  • 1
Страницы
  • 16-20
Ключевые слова
  • amantadine derivative; rimantadine; amantadine derivative; amino acid; Influenza A virus M2 viroporin; unclassified drug; viral protein; animal cell; antiviral resistance; antiviral susceptibility; antiviral therapy; Article; drug efficacy; drug mechanism; IC50; in vitro study; Influenza A virus (H1N1); MDCK cell line; monolayer culture; nonhuman; pandemic; peptide synthesis; physical chemistry; virostatic activity; virus inhibition; virus replication; virus strain; Alphainfluenzavirus; antiviral activity; antiviral resistance; Influenza A/California/07/2009(H1N1); Orthomyxoviridae
Издатель
  • FBSI Central Research Institute of Epidemiology of Rospotrebnadzor
Тип документа
  • journal article
Тип лицензии Creative Commons
  • CC
Правовой статус документа
  • Свободная лицензия
Источник
  • scopus