学科主题临床医学
In vitro inhibition of HBV replication by a novel compound, GLS4, and its efficacy against adefovir-dipivoxil-resistant HBV mutations
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
2012
DOI10.3851/IMP2152
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
WOS记录号WOS:000311080200003
项目编号91029741 ; 81171550 ; 81001072 ; 2008ZX10002-019 ; 2008ZX10002-008 ; 2007CB512906 ; 20110490250
资助机构National Natural Science Foundation of China ; National Key Sci-Tech Special Project of China ; National Basic Research Program ; China Postdoctoral Science Foundation Project
引用统计
被引频次:55[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/50947
专题北京大学第二临床医学院_北京大学肝病研究所
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
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GB/T 7714
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.
APA Wang, Xue-Yan.,Wei, Zhen-Man.,Wu, Guo-Yi.,Wang, Jiang-Hua.,Zhang, Ying-Jun.,...&Chen, Hong-Song.(2012).In vitro inhibition of HBV replication by a novel compound, GLS4, and its efficacy against adefovir-dipivoxil-resistant HBV mutations.ANTIVIRAL THERAPY,17(5),793-803.
MLA Wang, Xue-Yan,et al."In vitro inhibition of HBV replication by a novel compound, GLS4, and its efficacy against adefovir-dipivoxil-resistant HBV mutations".ANTIVIRAL THERAPY 17.5(2012):793-803.
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