title: Oleanolic acid and ursolic acid: novel hepatitis C virus antivirals that inhibit NS5B activity.
abstract: Hepatitis C virus (HCV) infects up to 170 million people worldwide and causes significant morbidity and mortality. Unfortunately, current therapy is only curative in approximately 50% of HCV patients and has adverse side effects, which warrants the need to develop novel and effective antivirals against HCV. We have previously reported that the Chinese herb Fructus Ligustri Lucidi (FLL) directly inhibited HCV NS5B RNA-dependent RNA polymerase (RdRp) activity (Kong et al., 2007). In this study, we found that the FLL aqueous extract strongly suppressed HCV replication. Further high-performance liquid chromatography (HPLC) analysis combined with inhibitory assays indicates that oleanolic acid and ursolic acid are two antiviral components within FLL aqueous extract that significantly suppressed the replication of HCV genotype 1b replicon and HCV genotype 2a JFH1 virus. Moreover, oleanolic acid and ursolic acid exhibited anti-HCV activity at least partly through suppressing HCV NS5B RdRp activity as noncompetitive inhibitors. Therefore, our results for the first time demonstrated that natural products oleanolic acid and ursolic acid could be used as potential HCV antivirals that can be applied to clinic trials either as monotherapy or in combination with other HCV antivirals.
authors: College of Bioscience and Engineering, Jiangxi Agricultural University, Nanchang, Jiangxi 330045, China. lingbaok@hotmail.com
authors: Lingbao
authors: L
authors: Kong
authors: Shanshan
authors: S
authors: Li
authors: Qingjiao
authors: Q
authors: Liao
authors: Yanni
authors: Y
authors: Zhang
authors: Ruina
authors: R
authors: Sun
authors: Xiangdong
authors: X
authors: Zhu
authors: Qinghua
authors: Q
authors: Zhang
authors: Jun
authors: J
authors: Wang
authors: Xiaoyu
authors: X
authors: Wu
authors: Xiaonan
authors: X
authors: Fang
authors: Ying
authors: Y
authors: Zhu
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D015536:Down-Regulation; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D006526:Hepatitis C / Q000821:virology*; D006801:Humans; D031659:Ligustrum / Q000737:chemistry*; D009828:Oleanolic Acid / Q000494:pharmacology*; D012093:Replicon / Q000187:drug effects; D014315:Triterpenes / Q000494:pharmacology*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects; D000097245:Ursolic Acid; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D004365:Drugs, Chinese Herbal; D009828:Oleanolic Acid; D014315:Triterpenes; D017361:Viral Nonstructural Proteins; D000097245:Ursolic Acid; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase