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Pan-genotypic Hepatitis C Virus Inhibition by Natural Products Derived from the Wild Egyptian Artichoke

Elsebai, Mahmoud Fahmi ; Koutsoudakis, George ; Saludes, Verónica ; Pérez-Vilaró, Gemma ; Turpeinen, Ari ; Mattila, Sampo ; Pirttilä, Anna Maria ; Fontaine-Vive, Fabien ; Mehiri, Mohamed ; Meyerhans, Andreas ; Diez, Juana Ou, J.-H. J.

Journal of virology, 2016-02, Vol.90 (4), p.1918-1930 [Peer Reviewed Journal]

United States: American Society for Microbiology

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Title:
Pan-genotypic Hepatitis C Virus Inhibition by Natural Products Derived from the Wild Egyptian Artichoke
Author: Elsebai, Mahmoud Fahmi ; Koutsoudakis, George ; Saludes, Verónica ; Pérez-Vilaró, Gemma ; Turpeinen, Ari ; Mattila, Sampo ; Pirttilä, Anna Maria ; Fontaine-Vive, Fabien ; Mehiri, Mohamed ; Meyerhans, Andreas ; Diez, Juana
Ou, J.-H. J.
Subjects: Antiviral Agents - isolation & purification ; Antiviral Agents - pharmacology ; Biological Products - isolation & purification ; Biological Products - pharmacology ; Cynara - chemistry ; Cynara cardunculus ; Extractes de plantes ; Farmacologia ; Hepacivirus - drug effects ; Hepacivirus - physiology ; Hepatitis C virus ; Lactones - isolation & purification ; Lactones - pharmacology ; Medicaments antivírics ; Plant Extracts - isolation & purification ; Plant Extracts - pharmacology ; Plant Leaves - chemistry ; Productes biològics ; Sesquiterpenes - isolation & purification ; Sesquiterpenes - pharmacology ; Vaccines and Antiviral Agents ; Virus de l'hepatitis C ; Virus Internalization - drug effects
Is Part Of: Journal of virology, 2016-02, Vol.90 (4), p.1918-1930
Notes: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
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. 2016. Pan-genotypic hepatitis C virus inhibition by natural products derived from the wild Egyptian artichoke. J Virol 90:1918–1930. doi:10.1128/JVI.02030-15.
Present address: George Koutsoudakis, Liver Unit, Hospital Clinic, Institut D′Investigacions Biomèdics August Pi i Sunyer (IDIBAPS), Barcelona Spain; Verónica Saludes, Microbiology Service, Germans Trias i Pujol University Hospital, Germans Trias i Pujol Health Sciences Research Institute (IGTP), Badalona, Spain, and Centro de Investigación Biomédica en Red (CIBER) en Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain.
M.F.E. and G.K. contributed equally to this article.
Description: 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. Because 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.
Publisher: United States: American Society for Microbiology
Language: English

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Pan-genotypic Hepatitis C Virus Inhibition by Natural Products Derived from the Wild Egyptian Artichoke

Elsebai, Mahmoud Fahmi ; Koutsoudakis, George ; Saludes, Verónica ; Pérez-Vilaró, Gemma ; Turpeinen, Ari ; Mattila, Sampo ; Pirttilä, Anna Maria ; Fontaine-Vive, Fabien ; Mehiri, Mohamed ; Meyerhans, Andreas ; Diez, Juana Ou, J.-H. J.

United States: American Society for Microbiology

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