Hemin potentiates the anti-hepatitis C virus activity of the antimalarial drug artemisinin.
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.
Paeshuyse
Jan
J
Rega Institute for Medical Research, Minderbroedersstraat 10, KU Leuven, B-3000 Leuven, Belgium.
Coelmont
Lotte
L
Vliegen
Inge
I
Van hemel
Johan
J
Vandenkerckhove
Jan
J
Peys
Eric
E
Sas
Benedikt
B
De Clercq
Erik
E
Neyts
Johan
J
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
D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; D006427:Hemin; C031327:artemisinin