title: Trachelogenin, a novel inhibitor of hepatitis C virus entry through CD81.
abstract: Although much progress has been made in antiviral agents against hepatitis C virus (HCV) in recent years, novel HCV inhibitors with improved efficacy, optimized treatment duration and more affordable prices are still urgently needed. Here, we report the identification of a natural plant-derived lignan, trachelogenin (TGN), as a potent entry inhibitor of HCV without genotype specificity, and with low cytotoxicity. TGN was extracted and purified from Caulis trachelospermi, a traditional Chinese herb with anti-inflammatory and analgesic effects. A crucial function of TGN was the inhibition of HCV entry during a post-binding step without affecting virus replication, translation, assembly and release. TGN blocked virus infection by interfering with the normal interactions between HCV glycoprotein E2 and the host entry factor CD81, which are key processes for valid virus entry. In addition, TGN diminished HCV cell-to-cell spread and exhibited additional synergistic effects when combined with IFN or telaprevir. In conclusion, this study highlights the effect of a novel HCV entry inhibitor, TGN, which has a target that differs from those of the current antiviral agents. Therefore, TGN is a potential candidate for future cocktail therapies to treat HCV-infected patients.
authors.affiliation: Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai 200433, PRChina.
authors.forename: Xi-Jing
authors.initials: XJ
authors.lastname: Qian
authors.affiliation: Department of Organic Chemistry, College of Pharmacy, Second Military Medical University, Shanghai 200433, PRChina.
authors.forename: Yong-Sheng
authors.initials: YS
authors.lastname: Jin
authors.affiliation: Department of Phytochemistry, College of Pharmacy, Second Military Medical University, Shanghai 200433, PRChina.
authors.forename: Hai-Sheng
authors.initials: HS
authors.lastname: Chen
authors.affiliation: Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai 200433, PRChina.
authors.forename: Qing-Qiang
authors.initials: QQ
authors.lastname: Xu
authors.affiliation: Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai 200433, PRChina.
authors.forename: Hao
authors.initials: H
authors.lastname: Ren
authors.affiliation: Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai 200433, PRChina.
authors.forename: Shi-Ying
authors.initials: SY
authors.lastname: Zhu
authors.affiliation: Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai 200433, PRChina.
authors.forename: Hai-Lin
authors.initials: HL
authors.lastname: Tang
authors.affiliation: Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai 200433, PRChina.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai 200433, PRChina.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai 200433, PRChina.
authors.forename: Zhong-Tian
authors.initials: ZT
authors.lastname: Qi
authors.affiliation: Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai 200433, PRChina.
authors.forename: Yong-Zhe
authors.initials: YZ
authors.lastname: Zhu
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D015394:Molecular Structure; D060225:Tetraspanin 28 / Q000235:genetics / Q000378:metabolism*; D019065:Virus Assembly / Q000187:drug effects; D053586:Virus Internalization / Q000187:drug effects*; D057074:Virus Release; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology
chemical_list: C554798:CD81 protein, human; D060225:Tetraspanin 28; C560586:trachelogenin; D015107:4-Butyrolactone