title: Hemin potentiates the anti-hepatitis C virus activity of the antimalarial drug artemisinin.
abstract: We report that the antimalarial drug artemisinin inhibits hepatitis C virus (HCV) replicon replication in a dose-dependent manner in two replicon constructs at concentrations that have no effect on the proliferation of the exponentially growing host cells. The 50% effective concentration (EC(50)) for inhibition of HCV subgenomic replicon replication in Huh 5-2 cells (luciferase assay) by artemisinin was 78+/-21 microM. Hemin, an iron donor, was recently reported to inhibit HCV replicon replication [mediated by inhibition of the viral polymerase (C. Fillebeen, A.M. Rivas-Estilla, M. Bisaillon, P. Ponka, M. Muckenthaler, M.W. Hentze, A.E. Koromilas, K. Pantopoulos, Iron inactivates the RNA polymerase NS5B and suppresses subgenomic replication of hepatitis C virus, J. Biol. Chem. 280 (2005) 9049-9057.)] at a concentration that had no adverse effect on the host cells. When combined, artemisinin and hemin resulted, over a broad concentration range, in a pronounced synergistic antiviral activity. Also at a concentration (2 microM) that alone had no effect on HCV replication, hemin still potentiated the anti-HCV activity of artemisinin.
authors.affiliation: Rega Institute for Medical Research, Minderbroedersstraat 10, KU Leuven, B-3000 Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Paeshuyse
authors.forename: Lotte
authors.initials: L
authors.lastname: Coelmont
authors.forename: Inge
authors.initials: I
authors.lastname: Vliegen
authors.forename: Johan
authors.initials: J
authors.lastname: Van hemel
authors.forename: Jan
authors.initials: J
authors.lastname: Vandenkerckhove
authors.forename: Eric
authors.initials: E
authors.lastname: Peys
authors.forename: Benedikt
authors.initials: B
authors.lastname: Sas
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
mesh_terms: D000962:Antimalarials / Q000494:pharmacology; D037621:Artemisinins / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006427:Hemin / Q000494:pharmacology*; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D020128:Inhibitory Concentration 50; D012093:Replicon / Q000187:drug effects; D012717:Sesquiterpenes / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; D006427:Hemin; C031327:artemisinin