Silibinin and related compounds are direct inhibitors of hepatitis C virus RNA-dependent RNA polymerase
| العنوان: | Silibinin and related compounds are direct inhibitors of hepatitis C virus RNA-dependent RNA polymerase |
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| المؤلفون: | Coralie Pallier, Abdelhakim Ahmed–Belkacem, Jean-Michel Pawlotsky, Laetitia Barbotte, Rozenn Brillet, Czeslaw Wychowski, Nazim Ahnou, Ralf–Torsten Pohl |
| المساهمون: | Guellaen, Georges, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut de biologie de Lille - IBL (IBLI), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Laboratoire de virologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Centre National de Référence Virus des hépatites B, C et Delta, Institut National de la Transfusion Sanguine [Paris] (INTS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Rottapharm/Madaus, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Droit et Santé |
| المصدر: | Gastroenterology Gastroenterology, 2010, 138 (3), pp.1112-22. ⟨10.1053/j.gastro.2009.11.053⟩ Gastroenterology, WB Saunders, 2010, 138 (3), pp.1112-22. ⟨10.1053/j.gastro.2009.11.053⟩ Gastroenterology, Elsevier, 2010, 138 (3), pp.1112-22. ⟨10.1053/j.gastro.2009.11.053⟩ |
| بيانات النشر: | HAL CCSD, 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Genotype, Hepatitis C virus, Silibinin, RNA-dependent RNA polymerase, Hepacivirus, Viral Nonstructural Proteins, Biology, Virus Replication, medicine.disease_cause, Antiviral Agents, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Interferon, Cell Line, Tumor, RNA polymerase, Drug Resistance, Viral, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Replicon, NS5B, Cell Proliferation, Nucleic Acid Synthesis Inhibitors, 030304 developmental biology, 0303 health sciences, Dose-Response Relationship, Drug, Hepatology, Gastroenterology, RNA, virus diseases, RNA-Dependent RNA Polymerase, Virology, Recombinant Proteins, digestive system diseases, 3. Good health, chemistry, Silybin, Mutation, 030211 gastroenterology & hepatology, Silymarin, medicine.drug |
| الوصف: | International audience; BACKGROUND & AIMS: Silymarin is a mixture of flavonolignans extracted from the milk thistle. Silymarin contains several molecules, including silibinin A, silibinin B, isosilibinin A, isosilibinin B, silicristin, and silidianin. Intravenous infusion of silibinin induces dose-dependent reduction of hepatitis C virus (HCV) RNA levels. The aim of this study was to test the principal isomers contained in silymarin preparations for their ability to inhibit HCV enzymatic functions and replication in different models. METHODS: The inhibitory activity of silymarin components was tested in HCV RNA-dependent RNA polymerase and NS3/4A protease enzyme assays. Their ability to inhibit replication of an HCV genotype 1b replicon model and the JFH1 infectious HCV model in cell culture was also studied. RESULTS: Silibinin A, silibinin B, their water-soluble dihydrogen succinate forms and Legalon SIL, a commercially available intravenous preparation of silibinin, inhibited HCV RNA-dependent RNA polymerase function, with inhibitory concentrations 50% of the order of 75-100 microM. Silibinin A and silibinin B also inhibited HCV genotype 1b replicon replication and HCV genotype 2a strain JFH1 replication in cell culture. None of these compounds inhibited HCV protease function. CONCLUSIONS: Silibinin A and silibinin B, as well as Legalon SIL, inhibit HCV replicon and JFH1 replication in cell culture. This effect is at least partly explained by the ability of these compounds to inhibit HCV RNA-dependent RNA polymerase activity. Our results provide a basis for the optimization and subsequent development of members of the Flavonoid family as specific HCV antivirals. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0016-5085 1528-0012 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e181feb92a26835988f58ea18bd02cc1Test https://www.hal.inserm.fr/inserm-00465965/documentTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e181feb92a26835988f58ea18bd02cc1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00165085 15280012 |
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