title: Pan-genotypic Hepatitis C Virus Inhibition by Natural Products Derived from the Wild Egyptian Artichoke.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt Department of Chemistry, University of Oulu, Oulu, Finland Nice Institute of Chemistry, UMR CNRS 7272, UFR of Sciences, University Nice Sophia Antipolis, France Department of Biology, University of Oulu, Oulu, Finland.
authors.forename: Mahmoud Fahmi
authors.initials: MF
authors.lastname: Elsebai
authors.affiliation: Molecular Virology Group, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: George
authors.initials: G
authors.lastname: Koutsoudakis
authors.affiliation: Molecular Virology Group, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Saludes
authors.affiliation: Molecular Virology Group, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Pérez-Vilaró
authors.affiliation: Department of Chemistry, University of Oulu, Oulu, Finland.
authors.forename: Ari
authors.initials: A
authors.lastname: Turpeinen
authors.affiliation: Department of Chemistry, University of Oulu, Oulu, Finland.
authors.forename: Sampo
authors.initials: S
authors.lastname: Mattila
authors.affiliation: Department of Biology, University of Oulu, Oulu, Finland.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Pirttilä
authors.affiliation: Nice Institute of Chemistry, UMR CNRS 7272, UFR of Sciences, University Nice Sophia Antipolis, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Fontaine-Vive
authors.affiliation: Nice Institute of Chemistry, UMR CNRS 7272, UFR of Sciences, University Nice Sophia Antipolis, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Mehiri
authors.affiliation: Infection Biology Group, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meyerhans
authors.affiliation: Molecular Virology Group, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain juana.diez@upf.edu.
authors.forename: Juana
authors.initials: J
authors.lastname: Diez
mesh_terms: D000998:Antiviral Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001688:Biological Products / Q000302:isolation & purification / Q000494:pharmacology*; D031942:Cynara / Q000737:chemistry*; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D007783:Lactones / Q000302:isolation & purification / Q000494:pharmacology; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology; D053586:Virus Internalization / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D001688:Biological Products; D007783:Lactones; D010936:Plant Extracts; D012717:Sesquiterpenes; C075687:cynaropicrin