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学科主题: 临床医学
题名:
In vitro inhibition of HBV replication by a novel compound, GLS4, and its efficacy against adefovir-dipivoxil-resistant HBV mutations
作者: Wang, Xue-Yan1,2; Wei, Zhen-Man3; Wu, Guo-Yi1; Wang, Jiang-Hua1; Zhang, Ying-Jun4; Li, Jing4; Zhang, Heng-Hui1; Xie, Xing-Wang1; Wang, Xian4; Wang, Zhao-He4; Wei, Lai1; Wang, Yu5; Chen, Hong-Song1
刊名: ANTIVIRAL THERAPY
发表日期: 2012
DOI: 10.3851/IMP2152
卷: 17, 期:5, 页:793-803
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Infectious Diseases ; Pharmacology & Pharmacy ; Virology
研究领域[WOS]: Infectious Diseases ; Pharmacology & Pharmacy ; Virology
关键词[WOS]: HEPATITIS-B-VIRUS ; PROTEIN-PROTEIN INTERACTIONS ; CORE PARTICLES ; CAPSIDS ; BAY-41-4109 ; LAMIVUDINE ; ANTIGEN ; MODEL
英文摘要:

Background: HBV infection continues to be an important worldwide cause of morbidity and mortality. Patients with chronic hepatitis B can be successfully treated using nucleoside/nucleotide analogues. However, drug-resistant HBV mutants frequently arise, leading to treatment failure and progression to liver disease. Here, we report the effects of GLS4, a non-nucleosidic inhibitor that exhibits a novel and highly specific anti-HBV activity. Methods: The median inhibitory concentrations (IC(50)s) of GLS4 on HBV were measured by Southern blotting. HBV capsid and core protein levels were detected by immunoblotting. To determine the antiviral activity of GLS4 against adefovir dipivoxil (ADV)-resistant HBV mutants, HepG2 cells transiently transfected with PUC-HBV1.2 plasmids that contained one of three major ADV-resistant mutations (rtA181T, rtA181V and rtN236T) were treated with GLS4. Intracellular HBV replicative intermediates were detected by Southern blotting. The effect on the in vitro assembly of HBV capsid protein was examined using dynamic light scattering and electron microscopy. Results: The IC50 of GLS4 was 0.012 mu M, which is significantly lower than that of lamivudine (0.325 mu M). Immunoblot analysis of HepG2.2.15 cells and transiently -transfected HepG2 cells indicated that GLS4 treatment interfered with the formation of core particles (assembly). The ADV-resistant HBV mutant strains were also sensitive to GLS4. Upon examining the in vitro assembly of HBV core protein 149 by electron microscopy, increased aberrant particles were observed after GLS4 treatment. Conclusions: GLS4 is a new and unique potential anti-HBV agent that possesses a different mechanism of action than existing therapeutic drugs.

语种: 英语
所属项目编号: 91029741 ; 81171550 ; 81001072 ; 2008ZX10002-019 ; 2008ZX10002-008 ; 2007CB512906 ; 20110490250
项目资助者: National Natural Science Foundation of China ; National Key Sci-Tech Special Project of China ; National Basic Research Program ; China Postdoctoral Science Foundation Project
WOS记录号: WOS:000311080200003
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/50947
Appears in Collections:北京大学第二临床医学院_北京大学肝病研究所_期刊论文

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作者单位: 1.Beihua Univ, Sch Publ Hlth, Jilin, Jilin, Peoples R China
2.Sunshine Lake Pharma Co Ltd, Dong Guan, Peoples R China
3.Peking Univ, Inst Hepatol, Peoples Hosp, Beijing 100871, Peoples R China
4.302nd Hosp Peoples Liberat Army, Ctr Clin Trials, Beijing, Peoples R China
5.Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China

Recommended Citation:
Wang, Xue-Yan,Wei, Zhen-Man,Wu, Guo-Yi,et al. In vitro inhibition of HBV replication by a novel compound, GLS4, and its efficacy against adefovir-dipivoxil-resistant HBV mutations[J]. ANTIVIRAL THERAPY,2012,17(5):793-803.
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