Abstract Title:

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

Abstract Source:

J Virol. 2015 Dec 9. Epub 2015 Dec 9. PMID: 26656684

Abstract Author(s):

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

Article Affiliation:

Mahmoud Fahmi Elsebai

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 Sinai Peninsula to treat hepatitis symptoms. Here, we isolated and characterized six compounds from the water extract of WEA and evaluated their HCV inhibition capacity in vitro. Importantly, two of these compounds namely grosheimol and cynaropicrin inhibited HCV with half maximal effective concentrations (EC50) in the low micromolar range. They inhibited HCV entry into target cells and were active both against 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: Because there is no preventive HCV vaccine available today, the discovery of novel anti-HCV cell entry inhibitors could help develop preventive measures of 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 was 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.

Study Type : In Vitro Study
Additional Links
Pharmacological Actions : Antiviral Agents : CK(1307) : AC(596)

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