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A novel phthalazinone derivative as a capsid assembly modulator inhibits hepatitis B virus expression

文献类型：期刊论文

作者Yang, Li5,6; Gong, Ying3,5; Liu, Feifei5; Chen, Wuhong1; Wang, Xinran5,7; Long, Guozhang1; Li, Heng3,5; Xiao, Fuling3,5; Lu, Mengji2; Hu, Youhong1,3,4
刊名ANTIVIRAL RESEARCH
出版日期2024
卷号221页码:14
关键词Hepatitis B virus Capsid assembly Phthalazinone derivatives Apoptosis
ISSN号0166-3542
DOI10.1016/j.antiviral.2023.105763
通讯作者Hu, Youhong(yhhu@simm.ac.cn) ; Tong, Xiankun(xktong@simm.ac.cn) ; Zuo, Jianping(jpzuo@simm.ac.cn)
英文摘要Development of new anti-hepatitis B virus (HBV) drugs that target viral capsid assembly is a very active research field. We identify a novel phthalazinone derivative, compound 5832, as a potent HBV inhibitor. In this study, we intend to elaborate the antiviral effect and mechanism of 5832 against HBV in vitro and in vivo. Compound 5832 treatment induces the formation of genome-free empty capsid by interfering with the core protein assembly domain, which significantly decreases the extracellular and intracellular HBV DNA. In the AAV-HBV transduced mouse model, 5832 suppresses serum HBV DNA after 4-week treatment, and decreases HBsAg and HBeAg levels. 5832 treatment also reduces intrahepatic HBV RNA, DNA and HBcAg levels. During the follow-up period after treatment withdrawal, serum antigen levels demonstrated no increase. We demonstrate 5832 treatment could active apoptotic signaling by elevating the expression of death receptor 5 (DR5), which participated in corresponding HBcAg-positive hepatocyte eradication. Phthalazinone derivative 5832 may serve as a promising antiHBV drug candidate to improve the treatment options for chronic HBV infection.
WOS关键词FAS-MEDIATED APOPTOSIS ; CIRCULAR DNA ; TRAIL ; REPLICATION ; PROTEIN ; LIGAND ; AT-61
资助项目National Natural Science Foundation of China[82104240] ; National Natural Science Foundation of China[81872725] ; Science and Technology Commission of Shanghai Municipality[20S11906200]
WOS研究方向Pharmacology & Pharmacy ; Virology
语种英语
WOS记录号WOS:001134986800001
出版者ELSEVIER
源URL[http://119.78.100.183/handle/2S10ELR8/308565]  
专题新药研究国家重点实验室
通讯作者Hu, Youhong; Tong, Xiankun; Zuo, Jianping
作者单位1.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
2.Univ Duisburg Essen, Univ Hosp Essen, Inst Virol, D-45122 Essen, Germany
3.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
4.UCAS, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, Lab Immunopharmacol, 555 ZuChongZhi Rd, Shanghai 201203, Peoples R China
6.Fudan Univ, Sch Basic Med Sci, Shanghai Frontiers Sci Ctr Pathogen Microorganisms, Key Lab Med Mol Virol MOE,NHC,CAMS, Shanghai 200032, Peoples R China
7.Nanjing Univ Chinese Med, Sch Chinese Mat Med, 138 Xianlin Rd, Nanjing 210023, Peoples R China
推荐引用方式
GB/T 7714		 Yang, Li,Gong, Ying,Liu, Feifei,et al. A novel phthalazinone derivative as a capsid assembly modulator inhibits hepatitis B virus expression[J]. ANTIVIRAL RESEARCH,2024,221:14.
APA Yang, Li.,Gong, Ying.,Liu, Feifei.,Chen, Wuhong.,Wang, Xinran.,...&Zuo, Jianping.(2024).A novel phthalazinone derivative as a capsid assembly modulator inhibits hepatitis B virus expression.ANTIVIRAL RESEARCH,221,14.
MLA Yang, Li,et al."A novel phthalazinone derivative as a capsid assembly modulator inhibits hepatitis B virus expression".ANTIVIRAL RESEARCH 221(2024):14.

入库方式： OAI收割

来源：上海药物研究所

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