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Artemisinin analogues as potent inhibitors of in vitro hepatitis C virus replication

(2013) PLOS ONE. 8(12).
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Abstract
We reported previously that Artemisinin (ART), a widely used anti-malarial drug, is an inhibitor of in vitro HCV subgenomic replicon replication. We here demonstrate that ART exerts its antiviral activity also in hepatoma cells infected with full length infectious HCV JFH-1. We identified a number of ART analogues that are up to 10-fold more potent and selective as in vitro inhibitors of HCV replication than ART. The iron donor Hemin only marginally potentiates the anti-HCV activity of ART in HCV-infected cultures. Carbon-centered radicals have been shown to be critical for the anti-malarial activity of ART. We demonstrate that carbon-centered radicals-trapping (the so-called TEMPO) compounds only marginally affect the anti-HCV activity of ART. This provides evidence that carbon-centered radicals are not the main effectors of the anti-HCV activity of the Artemisinin. ART and analogues may possibly exert their anti-HCV activity by the induction of reactive oxygen species (ROS). The combined anti-HCV activity of ART or its analogues with L-N-Acetylcysteine (L-NAC) [a molecule that inhibits ROS generation] was studied. L-NAC significantly reduced the in vitro anti-HCV activity of ART and derivatives. Taken together, the in vitro anti-HCV activity of ART and analogues can, at least in part, be explained by the induction of ROS; carbon-centered radicals may not be important in the anti-HCV effect of these molecules.
Keywords
ARTESUNATE, MALARIA, OXIDATIVE STRESS, PROTEASE INHIBITORS, PLASMODIUM-FALCIPARUM, DERIVATIVES, CELLS, RESISTANCE, THERAPY, POLYMERASE

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Chicago
Obeid, Susan, Jo Alen, Van Hung Nguyen, Van Cuong Pham, Philip Meuleman, Christophe Pannecouque, Thanh Nguyen Le, Johan Neyts, Wim Dehaen, and Jan Paeshuyse. 2013. “Artemisinin Analogues as Potent Inhibitors of in Vitro Hepatitis C Virus Replication.” Plos One 8 (12).
APA
Obeid, S., Alen, J., Nguyen, V. H., Pham, V. C., Meuleman, P., Pannecouque, C., Le, T. N., et al. (2013). Artemisinin analogues as potent inhibitors of in vitro hepatitis C virus replication. PLOS ONE, 8(12).
Vancouver
1.
Obeid S, Alen J, Nguyen VH, Pham VC, Meuleman P, Pannecouque C, et al. Artemisinin analogues as potent inhibitors of in vitro hepatitis C virus replication. PLOS ONE. 2013;8(12).
MLA
Obeid, Susan, Jo Alen, Van Hung Nguyen, et al. “Artemisinin Analogues as Potent Inhibitors of in Vitro Hepatitis C Virus Replication.” PLOS ONE 8.12 (2013): n. pag. Print.
@article{4314428,
  abstract     = {We reported previously that Artemisinin (ART), a widely used anti-malarial drug, is an inhibitor of in vitro HCV subgenomic replicon replication. We here demonstrate that ART exerts its antiviral activity also in hepatoma cells infected with full length infectious HCV JFH-1. We identified a number of ART analogues that are up to 10-fold more potent and selective as in vitro inhibitors of HCV replication than ART. The iron donor Hemin only marginally potentiates the anti-HCV activity of ART in HCV-infected cultures. Carbon-centered radicals have been shown to be critical for the anti-malarial activity of ART. We demonstrate that carbon-centered radicals-trapping (the so-called TEMPO) compounds only marginally affect the anti-HCV activity of ART. This provides evidence that carbon-centered radicals are not the main effectors of the anti-HCV activity of the Artemisinin. ART and analogues may possibly exert their anti-HCV activity by the induction of reactive oxygen species (ROS). The combined anti-HCV activity of ART or its analogues with L-N-Acetylcysteine (L-NAC) [a molecule that inhibits ROS generation] was studied. L-NAC significantly reduced the in vitro anti-HCV activity of ART and derivatives. Taken together, the in vitro anti-HCV activity of ART and analogues can, at least in part, be explained by the induction of ROS; carbon-centered radicals may not be important in the anti-HCV effect of these molecules.},
  articleno    = {e81783},
  author       = {Obeid, Susan and Alen, Jo and Nguyen, Van Hung and Pham, Van Cuong and Meuleman, Philip and Pannecouque, Christophe and Le, Thanh Nguyen and Neyts, Johan and Dehaen, Wim and Paeshuyse, Jan},
  issn         = {1932-6203},
  journal      = {PLOS ONE},
  keyword      = {ARTESUNATE,MALARIA,OXIDATIVE STRESS,PROTEASE INHIBITORS,PLASMODIUM-FALCIPARUM,DERIVATIVES,CELLS,RESISTANCE,THERAPY,POLYMERASE},
  language     = {eng},
  number       = {12},
  pages        = {6},
  title        = {Artemisinin analogues as potent inhibitors of in vitro hepatitis C virus replication},
  url          = {http://dx.doi.org/10.1371/journal.pone.0081783},
  volume       = {8},
  year         = {2013},
}

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