重庆医科大学汪凯的科学博客分享 http://blog.sciencenet.cn/u/Kwang02 重医感染性疾病分子生物学教育部重点实验室——汪凯的学术主页

博文

乙型肝炎病毒核衣壳抑制剂N-Sulfonylpiperidine-3-carboxamides inhibit HBV

已有 852 次阅读 2022-2-9 10:50 |系统分类:论文交流

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

Abstract

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.


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

关键词:乙型肝炎病毒;  核心蛋白; 核衣壳; 组装抑制剂; 抗病毒活性

Full text: https://www.mdpi.com/1999-4915/14/2/348  


衣壳抑制剂.jpg

 HBV核衣壳抑制剂筛选流程 


 Yang Yang(杨泱), Yu Yan(严宇), Jiaxin Yin, Jie Hu, Xuefei Cai, Jieli Hu, Jie Xia, Kai Wang, Ni Tang, and Luyi Huang. 2022. "Structure-Based Discovery of N-Sulfonylpiperidine-3-carboxamides as Novel Capsid Assembly Modulators for Potent Inhibition of HBV Replication" Viruses 14, no. 2: 348. https://doi.org/10.3390/v14020348 




https://blog.sciencenet.cn/blog-446272-1324579.html

上一篇:【分子生物学工具网址】氨基酸密码子优化等工具网站推荐
下一篇:新冠病毒的血清型 Towards SARS-CoV-2 serotypes?

0

评论 (0 个评论)

数据加载中...

Archiver|手机版|科学网 ( 京ICP备07017567号-12 )

GMT+8, 2022-6-28 11:13

Powered by ScienceNet.cn

Copyright © 2007- 中国科学报社

返回顶部