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A Novel Pyridazinone Derivative Inhibits Hepatitis B Virus Replication by Inducing Genome-Free Capsid Formation

文献类型：期刊论文

作者Wang, Ya-Juan1; Lu, Dong2; Xu, Yi-Bin1; Xing, Wei-Qiang2; Tong, Xian-Kun1; Wang, Gui-Feng1; Feng, Chun-Lan1; He, Pei-Lan1; Yang, Li1; Tang, Wei1
刊名ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
出版日期2015-11
卷号59期号:11页码:7061-7072
ISSN号0066-4804
DOI10.1128/AAC.01558-15
文献子类Article
英文摘要Here we first identified a novel pyridazinone derivative, compound 3711, as a nonnucleosidic hepatitis B virus (HBV) inhibitor in a cell model system. 3711 decreased extracellular HBV DNA levels by 50% (50% inhibitory concentration [IC50]) at 1.5 +/- 0.2 mu M and intracellular DNA levels at 1.9 +/- 0.1 mu M, which demonstrated antiviral activity at levels far below those associated with toxicity. Both the 3TC/ETV dually resistant L180M/M204I mutant and the adefovir (ADV)-resistant A181T/N236T mutant were as susceptible to 3711 as wild-type HBV. 3711 treatment induced the formation of genome-free capsids, a portion of which migrated faster on 1.8% native agarose gel. The induced genome-free capsids sedimented more slowly in isopycnic CsCl gradient centrifugation without significant morphological changes. 3711 treatment decreased levels of HBV DNA contained in both secreted enveloped virion and naked virus particles in supernatant. 3711 could interfere with capsid formation of the core protein (Cp) assembly domain. A Cp V124W mutant, which strengthens capsid interdimer interactions, recapitulated the effect of 3711 on capsid assembly. Pyridazinone derivative 3711, a novel chemical entity and HBV inhibitor, may provide a new opportunity to combat chronic HBV infection.
WOS关键词PHENYLPROPENAMIDE DERIVATIVES ; PARTICLES ; PROTEIN ; HBV ; CELLS ; NUCLEOCAPSIDS ; ENCAPSIDATION ; EXPRESSION ; INFECTION ; COMPOUND
资助项目National Nature Science Foundation of China (NSFC)[81322049] ; National Nature Science Foundation of China (NSFC)[31570166] ; National Program on Key Basic Research Project (973 Program)[2013CB911104] ; National Science Fund for Distinguished Young Scholars[81225022]
WOS研究方向Microbiology ; Pharmacology & Pharmacy
语种英语
出版者AMER SOC MICROBIOLOGY
WOS记录号WOS:000368238100047
源URL[http://119.78.100.183/handle/2S10ELR8/276333]  
专题药理学第一研究室
药物化学研究室
通讯作者Yang, Li
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Lab Immunopharmacol, Shanghai 200031, Peoples R China;
2.Chinese Acad Sci, Shanghai Inst Mat Med, Med Chem Lab, Shanghai 200031, Peoples R China;
3.Shanghai Univ Tradit Chinese Med, Lab Immunol & Virol, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Wang, Ya-Juan,Lu, Dong,Xu, Yi-Bin,et al. A Novel Pyridazinone Derivative Inhibits Hepatitis B Virus Replication by Inducing Genome-Free Capsid Formation[J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY,2015,59(11):7061-7072.
APA Wang, Ya-Juan.,Lu, Dong.,Xu, Yi-Bin.,Xing, Wei-Qiang.,Tong, Xian-Kun.,...&Zuo, Jian-Ping.(2015).A Novel Pyridazinone Derivative Inhibits Hepatitis B Virus Replication by Inducing Genome-Free Capsid Formation.ANTIMICROBIAL AGENTS AND CHEMOTHERAPY,59(11),7061-7072.
MLA Wang, Ya-Juan,et al."A Novel Pyridazinone Derivative Inhibits Hepatitis B Virus Replication by Inducing Genome-Free Capsid Formation".ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 59.11(2015):7061-7072.

入库方式： OAI收割

来源：上海药物研究所

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