Structure-Based Discovery of N-Sulfonylpiperidine-3-Carboxamides as Novel Capsid Assembly Modulators for Potent Inhibition of HBV Replication

作者全名："Yang, Yang; Yan, Yu; Yin, Jiaxin; Hu, Jie; Cai, Xuefei; Hu, Jieli; Xia, Jie; Wang, Kai; Tang, Ni; Huang, Luyi"

作者地址："[Yang, Yang; Yan, Yu; Yin, Jiaxin; Hu, Jie; Cai, Xuefei; Hu, Jieli; Xia, Jie; Wang, Kai; Tang, Ni; Huang, Luyi] Chongqing Med Univ, Affiliated Hosp 2, Key Lab Mol Biol Infect Dis, Dept Infect Dis,Inst Viral Hepatitis,Minist Educ, Chongqing 400010, Peoples R China"

通信作者："Tang, N; Huang, LY (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Key Lab Mol Biol Infect Dis, Dept Infect Dis,Inst Viral Hepatitis,Minist Educ, Chongqing 400010, Peoples R China."

来源：VIRUSES-BASEL

ESI学科分类：MICROBIOLOGY

WOS号：WOS:000764306700001

JCR分区：Q2

影响因子：4.7

年份：2022

卷号：14

期号：2

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结束页：　

文献类型：Article

关键词：hepatitis B virus; core protein; capsid; assembly modulator; antiviral activity

摘要："As a key element during HBV replication, a nucleocapsid is considered a promising target for the treatment of chronic hepatitis B. The present study aimed to identify small molecules as novel capsid assembly modulators with antiviral activity. Structure-based virtual screening of an integrated compound library led to the identification of several types of HBV inhibitors. Among these inhibitors, N-sulfonylpiperidine-3-carboxamides (SPCs) potently reduced the amount of secreted HBV DNA. Through structure-activity relationship studies, we identified an SPC derivative, namely, C-39, which exhibited the highest antiviral activity without causing cytotoxicity. Mechanism studies showed that C-39 dose-dependently inhibited the formation of HBV capsid, synthesis of cccDNA, e antigen (HBeAg), viral pregenomic RNA (pgRNA), and HBV DNA levels, thereby restraining HBV replication. In summary, SPCs represent a new class of capsid assembly modulators. Further optimization of SPCs is expected to obtain new antiviral drugs against HBV infection."

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