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

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 o...

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Autores principales:	Susan Obeid, Jo Alen, Van Hung Nguyen, Van Cuong Pham, Philip Meuleman, Christophe Pannecouque, Thanh Nguyen Le, Johan Neyts, Wim Dehaen, Jan Paeshuyse
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/73e0fc56ed274387bcb6e5c66d2f31bd
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spelling	oai:doaj.org-article:73e0fc56ed274387bcb6e5c66d2f31bd2021-11-18T08:42:29ZArtemisinin analogues as potent inhibitors of in vitro hepatitis C virus replication.1932-620310.1371/journal.pone.0081783https://doaj.org/article/73e0fc56ed274387bcb6e5c66d2f31bd2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24349127/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203We 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.Susan ObeidJo AlenVan Hung NguyenVan Cuong PhamPhilip MeulemanChristophe PannecouqueThanh Nguyen LeJohan NeytsWim DehaenJan PaeshuysePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e81783 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Susan Obeid Jo Alen Van Hung Nguyen Van Cuong Pham Philip Meuleman Christophe Pannecouque Thanh Nguyen Le Johan Neyts Wim Dehaen Jan Paeshuyse Artemisinin analogues as potent inhibitors of in vitro hepatitis C virus replication.
description	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.
format	article
author	Susan Obeid Jo Alen Van Hung Nguyen Van Cuong Pham Philip Meuleman Christophe Pannecouque Thanh Nguyen Le Johan Neyts Wim Dehaen Jan Paeshuyse
author_facet	Susan Obeid Jo Alen Van Hung Nguyen Van Cuong Pham Philip Meuleman Christophe Pannecouque Thanh Nguyen Le Johan Neyts Wim Dehaen Jan Paeshuyse
author_sort	Susan Obeid
title	Artemisinin analogues as potent inhibitors of in vitro hepatitis C virus replication.
title_short	Artemisinin analogues as potent inhibitors of in vitro hepatitis C virus replication.
title_full	Artemisinin analogues as potent inhibitors of in vitro hepatitis C virus replication.
title_fullStr	Artemisinin analogues as potent inhibitors of in vitro hepatitis C virus replication.
title_full_unstemmed	Artemisinin analogues as potent inhibitors of in vitro hepatitis C virus replication.
title_sort	artemisinin analogues as potent inhibitors of in vitro hepatitis c virus replication.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/73e0fc56ed274387bcb6e5c66d2f31bd
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Artemisinin analogues as potent inhibitors of in vitro hepatitis C virus replication.

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