可水解单宁（punicalagin，punicalin和geraniin）乙型肝炎病毒作为

StephenW

Antiviral Res. 2016 Aug 30. pii: S0166-3542(16)30022-5. doi: 10.1016/j.antiviral.2016.08.026. [Epub ahead of print]
Identification of hydrolyzable tannins (punicalagin, punicalin and geraniin) as novel inhibitors of hepatitis B virus covalently closed circular DNA.Liu C1, Cai D2, Zhang L1, Tang W1, Yan R2, Guo H3, Chen X4.
Author information

• 1State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 43001, Hubei, China.
• 2Department of Microbiology and Immunology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN 46202, USA.
• 3Department of Microbiology and Immunology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN 46202, USA. Electronic address: [email protected].
• 4State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 43001, Hubei, China. Electronic address: [email protected].
  

AbstractThe development of new agents to target HBV cccDNA is urgently needed because of the limitations of current available drugs for treatment of hepatitis B. By using a cell-based assay in which the production of HBeAg is in a cccDNA-dependent manner, we screened a compound library derived from Chinese herbal remedies for inhibitors against HBV cccDNA. Three hydrolyzable tannins, specifically punicalagin, punicalin and geraniin, emerged as novel anti-HBV agents. These compounds significantly reduced the production of secreted HBeAg and cccDNA in a dose-dependent manner in our assay, without dramatic alteration of viral DNA replication. Furthermore, punicalagin did not affect precore/core promoter activity, pgRNA transcription, core protein expression, or HBsAg secretion. By employing the cell-based cccDNA accumulation and stability assay, we found that these tannins significantly inhibited the establishment of cccDNA and modestly facilitated the degradation of preexisting cccDNA. Collectively, our results suggest that hydrolyzable tannins inhibit HBV cccDNA production via a dual mechanism through preventing the formation of cccDNA and promoting cccDNA decay, although the latter effect is rather minor. These hydrolyzable tannins may serve as lead compounds for the development of new agents to cure HBV infection.
Copyright © 2016. Published by Elsevier B.V.


KEYWORDS: Antiviral; HBV; Hydrolyzable tannins; cccDNA

PMID:27591143DOI:10.1016/j.antiviral.2016.08.026

StephenW

抗病毒水库。 2016年30月PII：S0166-3542（16）30022-5。 DOI：10.1016 / j.antiviral.2016.08.026。 [打印EPUB提前]
可水解单宁（punicalagin，punicalin和geraniin）乙型肝炎病毒作为新型抑制剂的鉴定共价闭合环状DNA。
刘C1，D2蔡，张L1，唐W1，燕R2，郭H3，陈X4。
作者信息

    武汉病毒研究所，中国院士，武汉43001，湖北省，中国病毒学国家重点实验室。
    微生物学和免疫学，医学印第安纳大学医学院，635 Barnhill驱动器，印第安纳波利斯，46202，USA教研室。
    微生物学和免疫学，医学印第安纳大学医学院，635 Barnhill驱动器，印第安纳波利斯，46202，USA的3Department。电子地址：[email protected]。
    武汉病毒研究所，中国院士，武汉43001，湖北省，中国病毒学4State重点实验室。电子地址：[email protected]。

抽象

的新药物开发的目标是迫切需要的，因为当前可用的药物用于治疗乙型肝炎的通过使用基于细胞的测定，其中生产的HBeAg的是在一个cccDNA的依赖性的局限性HBV cccDNA的，我们筛选一从中国的草药推导出抗HBV cccDNA的抑制剂的化合物库。三水解单宁，具体punicalagin，punicalin和geraniin，成为新的抗HBV药物。这些化合物显著降低了生产分​​泌HBeAg和cccDNA的在我们的测定中以剂量依赖性方​​式，没有病毒DNA复制的戏剧性变化。此外，punicalagin并不影响前核心/核心启动子的活性，pgRNA转录，核心蛋白的表达，或HBsAg的分泌。通过采用基于细胞的cccDNA的积累和稳定性测定中，我们发现，这些单宁显著抑制建立的cccDNA的和适度促进先前存在的cccDNA的降解。总的来说，我们的研究结果表明，可水解的单宁抑制经由通过防止cccDNA的形成和促进的cccDNA衰变双重机制HBV cccDNA的生产，虽然后者的影响是相当小的。这些水解单宁酸可以用来为新发展代理商作为先导化合物治疗HBV感染。

版权所有©2016年出版由Elsevier B.V.
关键词：

抗病毒;乙肝病毒;水解单宁; cccDNA的

结论：
    27591143
DOI：
    10.1016 / j.antiviral.2016.08.026

只一个衣

好消息。