Primary identification of compounds targeting hepatitis B virus capsid formation from the FDA approved drugs

Yi YUAN; Zhiying LI; Xiafei WEI; Jing SHEN; Jieli HU

doi:10.16016/j.1000-5404.201811214

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Primary identification of compounds targeting hepatitis B virus capsid formation from the FDA approved drugs

Basic Medicine | 更新时间：2026-01-09

- Primary identification of compounds targeting hepatitis B virus capsid formation from the FDA approved drugs
- Journal of Third Military Medical University Vol. 41, Issue 11, Pages: 1059-1064(2019)
- 作者机构：
  
  1.400016 重庆，重庆医科大学感染性疾病分子生物学教育部重点实验室
  2.400010 重庆，重庆医科大学附属第二医院消化内科
- 作者简介：
- 基金信息：
  
  the National Natural Science Foundation of China(81671997);the National Natural Science Foundation of China(81871635)
- DOI：10.16016/j.1000-5404.201811214
  CLC： R373.21;R95;R965.1
- Received：29 November 2018，
  
  Revised：2019-01-25，
  
  Published：15 June 2019
- 稿件说明：
移动端阅览
Yi YUAN, Zhiying LI, Xiafei WEI, et al. Primary identification of compounds targeting hepatitis B virus capsid formation from the FDA approved drugs[J]. Journal of Third Military Medical University, 2019, 41(11): 1059-1064.
DOI：

Yi YUAN, Zhiying LI, Xiafei WEI, et al. Primary identification of compounds targeting hepatitis B virus capsid formation from the FDA approved drugs[J]. Journal of Third Military Medical University, 2019, 41(11): 1059-1064. DOI： 10.16016/j.1000-5404.201811214.

摘要

目的

从FDA已批准的药物库中，筛选可以干扰乙肝病毒核衣壳形成的药物。

方法

利用细胞模型SRluc-HBc6，通过分段荧光素酶互补实验来指示二聚体的形成，筛选靶向HBV核心蛋白二聚体形成的药物；对初筛出来的候选化合物，用颗粒凝胶电泳分析法鉴定其对HBV核衣壳形成的影响；用Southern blot方法鉴定候选药物对HBV DNA复制的影响。

结果

利用SRluc-HBc6细胞模型筛选了FDA批准的1 434种药物，第1轮筛选鉴定到5种药物：苯丁酸氮芥(Chlorambucil)、克拉屈滨(Cladribine)、亚甲蓝(Methylene Blue)、索拉菲尼(Sorafenib)、瑞格菲尼(Regorafenib)；进一步测试发现，苯丁酸氮芥可以减少HBV核心蛋白和核衣壳的形成，抑制HepAD38细胞中HBV DNA的复制。

结论

苯丁酸氮芥通过减少HBV核心二聚体和衣壳的形成来抑制HBV DNA的复制。

Abstract

Objective

To identify the candidates targeting capsid formation of HBV by screening a FDA approved drug library.

Methods

SRluc-HBc6 cells

which indicates the formation of HBc dimers by the split luciferase complementation (SLC)

were used as the 1st round screening model. Compounds identified by the 1st round screening were tested for their ability to inhibit the formation of capsid by using particle gel assay. Southern blotting was employed to detect the anti-HBV activity of these compounds on the replication of HBV DNA.

Results

According to the Rluc activities of SRluc-HBc6 cells

5 candidates were screened out of 1 434 drugs in the first round screening. They are chlorambucil

cladribine

methylene blue

sorafenib

and regorafenib. Further tests showed that chlorambucil inhibited the replication of HBV DNA in HepAD38 cells by reducing the formation of HBV core dimers and capsids.

Conclusion

Chlorambucil inhibit HBV DNA replication

in vitro

by reducing HBV core dimers and the formation of capsid.

关键词

Keywords

references

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