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[Adamantan derivatives capable of inhibiting the reproduction of a Rimantadine resistant strain of influenza A(H1N1)pdm09 virus (Influenza A virus, Alphainfluenzavirus, Orthomyxoviridae).]
- Source :
-
Voprosy virusologii [Vopr Virusol] 2020; Vol. 65 (1), pp. 16-20. - Publication Year :
- 2020
-
Abstract
- 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 purpose of the study is to identify the antiviral properties of new adamantanum derivatives to the pandemic strain of influenza A virus in vitro.<br />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.<br />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 (IС <subscript>50</subscript> ) ranging from 0.5 to 2.5 мкM, which is generally a good indicator for the Rimantadine/Amantadine resistant strain.<br />Discussion: The values of the IС <subscript>50</subscript> 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.<br />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.<br />Competing Interests: The authors declare no conflict of interest.
- Subjects :
- Adamantane analogs & derivatives
Animals
Dogs
Humans
Influenza A Virus, H1N1 Subtype drug effects
Influenza A Virus, H1N1 Subtype genetics
Influenza A Virus, H1N1 Subtype pathogenicity
Influenza, Human genetics
Influenza, Human virology
Madin Darby Canine Kidney Cells
Mutation
Rimantadine adverse effects
Rimantadine pharmacology
Adamantane pharmacology
Drug Resistance, Viral drug effects
Influenza, Human drug therapy
Virus Replication drug effects
Subjects
Details
- Language :
- Russian
- ISSN :
- 2411-2097
- Volume :
- 65
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Voprosy virusologii
- Publication Type :
- Academic Journal
- Accession number :
- 32496716
- Full Text :
- https://doi.org/10.36233/0507-4088-2020-65-1-16-20