Trachelogenin, a novel inhibitor of hepatitis C virus entry through CD81

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 lign...

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Published in:Journal of general virology 2016-05, Vol.97 (5), p.1134-1144
Main Authors: Qian, Xi-Jing, Jin, Yong-Sheng, Chen, Hai-Sheng, Xu, Qing-Qiang, Ren, Hao, Zhu, Shi-Ying, Tang, Hai-Lin, Wang, Yan, Zhao, Ping, Qi, Zhong-Tian, Zhu, Yong-Zhe
Format: Article
Language:English
Subjects:
4-Butyrolactone - analogs & derivatives
4-Butyrolactone - pharmacology
Dose-Response Relationship, Drug
Genotype
Hepacivirus - genetics
Hepacivirus - physiology
Hepatitis C virus
Hepatocytes - virology
Humans
Molecular Structure
Tetraspanin 28 - genetics
Tetraspanin 28 - metabolism
Virus Assembly - drug effects
Virus Internalization - drug effects
Virus Release
Virus Replication - drug effects
Virus Replication - physiology
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Summary: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.
ISSN:0022-1317
1465-2099
DOI:10.1099/jgv.0.000432