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Pan-genotypic hepatitis C virus inhibition by natural products derived from the wild Egyptian artichoke

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dc.contributor.author Elsebai, Mahmoud Fahmi
dc.contributor.author Koutsoudakis, George
dc.contributor.author Saludes, Verónica
dc.contributor.author Pérez Vilaró, Gemma, 1985-
dc.contributor.author Turpeinen, Ari
dc.contributor.author Mattila, Sampo
dc.contributor.author Pirttilä, Anna Maria
dc.contributor.author Fontaine, Fabien
dc.contributor.author Mehiri, Mohamed
dc.contributor.author Meyerhans, Andreas
dc.contributor.author Díez Antón, Juana, 1962-
dc.date.accessioned 2017-02-03T08:09:17Z
dc.date.available 2017-02-03T08:09:17Z
dc.date.issued 2016
dc.identifier.citation Elsebai MF, Koutsoudakis G, Saludes V, Pérez-Vilaró G, Turpeinen A, Mattila S, Pirttilä AM, Fontaine-Vive F, Mehiri M, Meyerhans A, Diez J. Pan-genotypic hepatitis C virus inhibition by natural products derived from the wild Egyptian artichoke. J Virol. 2016; 90(4): 1918-30. DOI: 10.1128/JVI.02030-15
dc.identifier.issn 0022-538X
dc.identifier.uri http://hdl.handle.net/10230/28044
dc.description.abstract Hepatitis C virus (HCV) infection is the leading cause of chronic liver diseases. Water extracts of the leaves of the wild Egyptian artichoke (WEA) [Cynara cardunculus L. var. sylvestris (Lam.) Fiori] have been used for centuries in the Sinai Peninsula to treat hepatitis symptoms. Here we isolated and characterized six compounds from the water extracts of WEA and evaluated their HCV inhibition capacities in vitro. Importantly, two of these compounds, grosheimol and cynaropicrin, inhibited HCV with half-maximal effective concentrations (EC50s) in the low micromolar range. They inhibited HCV entry into target cells and were active against both cell-free infection as well as cell-cell transmission. Furthermore, the antiviral activity of both compounds was pan-genotypic as HCV genotypes 1a, 1b, 2b, 3a, 4a, 5a, 6a, and 7a were inhibited. Thus, grosheimol and cynaropicrin are promising candidates for the development of new pan-genotypic entry inhibitors of HCV infection. IMPORTANCE:/nBecause there is no preventive HCV vaccine available today, the discovery of novel anti-HCV cell entry inhibitors could help develop preventive measures against infection. The present study describes two compounds isolated from the wild Egyptian artichoke (WEA) with respect to their structural elucidation, absolute configuration, and quantitative determination. Importantly, both compounds inhibited HCV infection in vitro. The first compound was an unknown molecule, and it was designated "grosheimol," while the second compound is the known molecule cynaropicrin. Both compounds belong to the group of sesquiterpene lactones. The mode of action of these compounds occurred during the early steps of the HCV life cycle, including cell-free and cell-cell infection inhibition. These natural compounds present promising candidates for further development into anti-HCV therapeutics.
dc.description.sponsorship This work was supported by FEDER and the Spanish Ministry of Economy and Competitiveness through grants BFU 2013-44629-R and SAF2013-46077-R and the Maria de Maeztu Programme for Units of Excellence in R&D (MDM-2014-0370)
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher American Society for Microbiology
dc.rights © American Society for Microbiology
dc.subject.other Medicaments antivírics
dc.subject.other Productes biològics
dc.subject.other Farmacologia
dc.subject.other Virus de l'hepatitis C
dc.subject.other Extractes de plantes
dc.title Pan-genotypic hepatitis C virus inhibition by natural products derived from the wild Egyptian artichoke
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1128/JVI.02030-15
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/acceptedVersion


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