A Novel Pyridazinone Derivative Inhibits Hepatitis B Virus Replication by Inducing Genome-Free Capsid Formation | |
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 |
2015-11 | |
卷号 | 59期号:11页码:7061-7072 |
ISSN号 | 0066-4804 |
DOI | 10.1128/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. |
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关键词 | PHENYLPROPENAMIDE DERIVATIVES ; PARTICLES ; PROTEIN ; HBV ; CELLS ; NUCLEOCAPSIDS ; ENCAPSIDATION ; EXPRESSION ; INFECTION ; COMPOUND |
WOS研究方向 | Microbiology ; Pharmacology & Pharmacy |
语种 | 英语 |
出版者 | AMER SOC MICROBIOLOGY |
WOS记录号 | WOS:000368238100047 |
内容类型 | 期刊论文 |
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. |
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