中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 国家新药筛选中心
热门
Isothiafludine, a novel non-nucleoside compound, inhibits hepatitis B virus replication through blocking pregenomic RNA encapsidation

文献类型：期刊论文

作者Yang, Li2; Shi, Li-ping2; Chen, Hai-jun1; Tong, Xian-kun2; Wang, Gui-feng2; Zhang, Yang-ming1; Wang, Wen-long1; Feng, Chun-lan2; He, Pei-lan2; Zhu, Feng-hua2
刊名ACTA PHARMACOLOGICA SINICA
出版日期2014-03
卷号35期号:3页码:410-418
关键词hepatitis B virus replication capsid assembly pregenomic RNA non-nucleoside compound isothiafludine lamivudine adefovir entecavir
ISSN号1671-4083
DOI10.1038/aps.2013.175
文献子类Article
英文摘要Aim: To investigate the action of isothiafludine (NZ-4), a derivative of bis-heterocycle tandem pairs from the natural product leucamide A, on the replication cycle of hepatitis B virus (HBV) in vitro and in vivo. Methods: HBV replication cycle was monitored in HepG2.2.15 cells using qPCR, qRT-PCR, and Southern and Northern blotting. HBV protein expression and capsid assembly were detected using Western blotting and native agarose gel electrophoresis analysis. The interaction of pregenomic RNA (pgRNA) and the core protein was investigated by RNA immunoprecipitation. To evaluate the anti-HBV effect of NZ-4 in vivo, DHBV-infected ducks were orally administered NZ-4 (25, 50 or 100 mg.kg(-1).d(-1)) for 15 d. Results: NZ-4 suppressed intracellular HBV replication in HepG2.2.15 cells with an IC50 value of 1.33 mu mol/L, whereas the compound inhibited the cell viability with an IC50 value of 50.4 mu mol/L. Furthermore, NZ-4 was active against the replication of various drug-resistant HBV mutants, including 3TC/ETV-dual-resistant and ADV-resistant HBV mutants. NZ-4 (5, 10, and 20 mu mol/L) concentration-dependently reduced the encapsidated HBV pgRNA, resulting in the assembly of replication-deficient capsids in HepG2.2.15 cells. Oral administration of NZ-4 dose-dependently inhibited DHBV DNA replication in the DHBV-infected ducks. Conclusion: NZ-4 inhibits HBV replication by interfering with the interaction between pgRNA and HBcAg in the capsid assembly process, thus increasing the replication-deficient HBV capsids. Such mechanism of action might provide a new therapeutic strategy to combat HBV infection.
WOS关键词LIFE-CYCLE ; SURFACE-ANTIGEN ; NUCLEOCAPSIDS ; PROTEIN ; CELLS
资助项目Chinese Academy of Sciences (CAS) Knowledge Innovation Project[KSCX1-YW-10-03] ; National 863 Program Fund[2008AA02Z431] ; National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program"[2009ZX09102-024] ; National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program"[2012ZX09101-113]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
CSCD记录号CSCD:5067885
WOS记录号WOS:000332467200012
出版者ACTA PHARMACOLOGICA SINICA
源URL[http://119.78.100.183/handle/2S10ELR8/277173]  
专题国家新药筛选中心
中科院受体结构与功能重点实验室
新药研究国家重点实验室
药理学第一研究室
通讯作者Nan, Fa-jun
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Chinese Natl Ctr Drug Screening, Shanghai 201203, Peoples R China;
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Lab Immunopharmacol, Shanghai 201203, Peoples R China;
3.Tongji Med Coll, Tongji Hosp, Wuhan 430030, Peoples R China
推荐引用方式
GB/T 7714		 Yang, Li,Shi, Li-ping,Chen, Hai-jun,et al. Isothiafludine, a novel non-nucleoside compound, inhibits hepatitis B virus replication through blocking pregenomic RNA encapsidation[J]. ACTA PHARMACOLOGICA SINICA,2014,35(3):410-418.
APA Yang, Li.,Shi, Li-ping.,Chen, Hai-jun.,Tong, Xian-kun.,Wang, Gui-feng.,...&Zuo, Jian-ping.(2014).Isothiafludine, a novel non-nucleoside compound, inhibits hepatitis B virus replication through blocking pregenomic RNA encapsidation.ACTA PHARMACOLOGICA SINICA,35(3),410-418.
MLA Yang, Li,et al."Isothiafludine, a novel non-nucleoside compound, inhibits hepatitis B virus replication through blocking pregenomic RNA encapsidation".ACTA PHARMACOLOGICA SINICA 35.3(2014):410-418.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。