基于氨磺酰苯甲酰胺的衣壳装配调节剂，选择性抑制乙型肝

StephenW

Sulfamoylbenzamide-based Capsid Assembly Modulators for Selective Inhibition of Hepatitis B Viral Replication
Yeon Hee Lee  1   2 , Hyeon-Min Cha  1   3 , Jun Yeon Hwang  1 , So Yeong Park  1   2 , Avinash G Vishakantegowda  1   2 , Ali Imran  1 , Joo-Youn Lee  1 , Yoon-Sun Yi  4 , Sangmi Jun  4 , Ga Hyeon Kim  5   6 , Hyo Jin Kang  6 , Sang J Chung  5   6 , Meehyein Kim  1   3 , Hyejin Kim  1 , Soo Bong Han  1   2
Affiliations
Affiliations

    1
    Therapeutics & Biotechnology Division, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea.
    2
    Department of Medicinal Chemistry and Pharmacology, University of Science & Technology, Daejeon 34113, Republic of Korea.
    3
    Graduate School of New Drug Discovery and Development, Chungnam National University, Daejeon 34134, Republic of Korea.
    4
    Center for Research Equipment, Korea Basic Science Institute, Cheongju 28119, Republic of Korea.
    5
    School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
    6
    AbTis Co. Ltd. Suwon Venture Valley II, 142-10, Saneop-ro 156, Gwonseon-gu, Suwon 16648, Republic of Korea.

    PMID: 33603970 PMCID: PMC7883466 (available on 2022-02-11) DOI: 10.1021/acsmedchemlett.0c00606

Abstract

As the spread of infections caused by hepatitis B virus (HBV) threatens public health worldwide, investigations from multiple perspectives and of various mechanisms of action are urgently required to increase the HBV cure rate. Targeting the encapsidation of the nuclear capsid protein (core protein, HBc) has emerged as an attractive strategy for inhibiting the viral assembly process; however, a drug targeting this mechanism has not yet been approved. We synthesized novel sulfamoylbenzamides (SBAs) as capsid assembly modulators of HBV and found that the effects and safety profiles of compounds 3 and 8 have potential therapeutic applicability against HBV. The formation of tubular particles was time-dependent in the presence of 3, indicating a new mode of protein assembly by SBA compounds. Our findings provide a new entity for developing safe and efficient treatments for HBV infection.

© 2021 American Chemical Society.

StephenW

基于氨磺酰苯甲酰胺的衣壳装配调节剂，选择性抑制乙型肝炎病毒复制。
李妍熙1 2，贤敏茶1 3，俊妍黄1，苏荣公园1 2，阿维纳什·G·维沙康塔哥达1 2，阿里·伊姆兰1，李若英1，尹舜义4，尚米6，佳贤金5 6，孝真康6，尚志忠5 6，美妍金1 3，金惠珍1，秀凤汉1 2
隶属关系
隶属关系

    1个
    韩国化学技术研究所治疗​​与生物技术处，韩国大田34114。
    2
    科学技术大学药物化学与药理学系，韩国大田34113。
    3
    忠南国立大学新药发现与开发研究生院，韩国大田34134。
    4
    韩国基础科学研究所研究设备中心，韩国清州市28119。
    5
    成均馆大学药学院，大韩民国水原16419。
    6
    AbTis Co. Ltd.韩国水原市水原区广善区Saneop-ro 156 142-10，水源创业谷II，水坝16648，大韩民国。

    PMID：33603970 PMCID：PMC7883466（2022-02-11可用）DOI：10.1021 / acsmedchemlett.0c00606

抽象的

由于由乙型肝炎病毒（HBV）引起的感染扩散威胁着全世界的公共卫生，迫切需要从多种角度和各种作用机制进行研究，以提高HBV的治愈率。针对核衣壳蛋白（核心蛋白，HBc）的衣壳化已经成为抑制病毒装配过程的一种有吸引力的策略。但是，针对这种机制的药物尚未获得批准。我们合成了新型的氨磺酰苯甲酰胺（SBA）作为乙肝病毒的衣壳装配调节剂，发现化合物3和8的作用和安全性对乙肝病毒具有潜在的治疗适用性。在3的存在下，管状颗粒的形成是时间依赖性的，这表明SBA化合物具有新的蛋白质组装模式。我们的发现为开发安全有效的HBV感染治疗提供了新的条件。

©2021美国化学会。