title: A polyphenol rich plant extract, CYSTUS052, exerts anti influenza virus activity in cell culture without toxic side effects or the tendency to induce viral resistance.
abstract: Infections with influenza A viruses still pose a major threat to humans and several animal species. The occurrence of highly pathogenic avian influenza viruses of the H5N1 subtype capable to infect and kill humans highlights the urgent need for new and efficient countermeasures against this viral disease. Here we demonstrate that a polyphenol rich extract (CYSTUS052) from the Mediterranean plant Cistus incanus exerts a potent anti-influenza virus activity in A549 or MDCK cell cultures infected with prototype avian and human influenza strains of different subtypes. CYSTUS052 treatment resulted in a reduction of progeny virus titers of up to two logs. At the effective dose of 50 microg/ml the extract did not exhibit apparent harming effects on cell viability, metabolism or proliferation, which is consistent with the fact that these plant extracts are already used in traditional medicine in southern Europe for centuries without any reported complications. Viruses did not develop resistance to CYSTUS052 when compared to amantadine that resulted in the generation of resistant variants after only a few passages. On a molecular basis the protective effect of CYSTUS052 appears to be mainly due to binding of the polymeric polyphenol components of the extract to the virus surface, thereby inhibiting binding of the hemagglutinin to cellular receptors. Thus, a local application of CYSTUS052 at the viral entry routes may be a promising approach that may help to protect from influenza virus infections.
authors.affiliation: Institute of Molecular Virology, ZMBE, Westfaelische-Wilhelms-Universitaet, Von Esmarch-Str. 56, D-48159 Muenster, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Ehrhardt
authors.forename: Eike R
authors.initials: ER
authors.lastname: Hrincius
authors.forename: Virginia
authors.initials: V
authors.lastname: Korte
authors.forename: Igor
authors.initials: I
authors.lastname: Mazur
authors.forename: Karoline
authors.initials: K
authors.lastname: Droebner
authors.forename: Anne
authors.initials: A
authors.lastname: Poetter
authors.forename: Stephan
authors.initials: S
authors.lastname: Dreschers
authors.forename: Mirko
authors.initials: M
authors.lastname: Schmolke
authors.forename: Oliver
authors.initials: O
authors.lastname: Planz
authors.forename: Stephan
authors.initials: S
authors.lastname: Ludwig
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D001717:Birds; D002460:Cell Line; D002957:Citrus; D004285:Dogs; D024882:Drug Resistance, Viral; D005419:Flavonoids; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects; D053126:Influenza A Virus, H7N7 Subtype / Q000187:drug effects; D009980:Influenza A virus / Q000187:drug effects*; D005585:Influenza in Birds / Q000821:virology*; D007251:Influenza, Human / Q000821:virology*; D010636:Phenols; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D059808:Polyphenols; D012692:Serial Passage
chemical_list: D000998:Antiviral Agents; D005419:Flavonoids; D010636:Phenols; D010936:Plant Extracts; D059808:Polyphenols