ADS-J21 is a novel HIV-1 entry inhibitor targeting gp41

IF 4.8 Q1 MICROBIOLOGY Current Research in Microbial Sciences Pub Date : 2024-01-01 DOI:10.1016/j.crmicr.2024.100260

Ruiying Liang , Dou Dou , Chunying Wang , Shanshan Huo , Yang Wu , Juan Wang , Zhengsen Yu , Shuomin Zhang , Jingjing Xu , Yue Liu , Peng Liu , Shibo Jiang , Fei Yu

{"title":"ADS-J21 is a novel HIV-1 entry inhibitor targeting gp41","authors":"Ruiying Liang , Dou Dou , Chunying Wang , Shanshan Huo , Yang Wu , Juan Wang , Zhengsen Yu , Shuomin Zhang , Jingjing Xu , Yue Liu , Peng Liu , Shibo Jiang , Fei Yu","doi":"10.1016/j.crmicr.2024.100260","DOIUrl":null,"url":null,"abstract":"<div><p>HIV-1 envelope glycoprotein gp41 mediates fusion between HIV-1 and host cell membranes, making inhibitors of gp41 attractive anti-HIV drugs. We previously reported an efficient HIV-1 fusion inhibitor, ADS-J1, with a Y-shaped structure. Here, we discovered a new compound, ADS-J21, with a Y-shaped structure similar to that of ADS-J1 but with a lower molecular weight. Moreover, ADS-J21 exhibited effective anti-HIV-1 activity against divergent HIV-1 strains <em>in vitro</em>, including several HIV-1 laboratory-adapted strains and primary isolates with different subtypes (clades A to F) and tropisms (X4 or R5). Mechanistic studies have demonstrated that ADS-J21 blocks the formation of the gp41 six-helix bundle (6-HB) by targeting conserved amino acids Lys35 and Trp32. These findings suggest that ADS-J21 can be used as a new lead compound for further optimization in the development of a small-molecule fusion inhibitor.</p></div>","PeriodicalId":34305,"journal":{"name":"Current Research in Microbial Sciences","volume":"7 ","pages":"Article 100260"},"PeriodicalIF":4.8000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666517424000427/pdfft?md5=66eb91c4adefa23816fce7efab38647e&pid=1-s2.0-S2666517424000427-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Research in Microbial Sciences","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2666517424000427","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MICROBIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

HIV-1 envelope glycoprotein gp41 mediates fusion between HIV-1 and host cell membranes, making inhibitors of gp41 attractive anti-HIV drugs. We previously reported an efficient HIV-1 fusion inhibitor, ADS-J1, with a Y-shaped structure. Here, we discovered a new compound, ADS-J21, with a Y-shaped structure similar to that of ADS-J1 but with a lower molecular weight. Moreover, ADS-J21 exhibited effective anti-HIV-1 activity against divergent HIV-1 strains in vitro, including several HIV-1 laboratory-adapted strains and primary isolates with different subtypes (clades A to F) and tropisms (X4 or R5). Mechanistic studies have demonstrated that ADS-J21 blocks the formation of the gp41 six-helix bundle (6-HB) by targeting conserved amino acids Lys35 and Trp32. These findings suggest that ADS-J21 can be used as a new lead compound for further optimization in the development of a small-molecule fusion inhibitor.

Abstract Image

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

ADS-J21 是针对 gp41 的新型 HIV-1 进入抑制剂

HIV-1 包膜糖蛋白 gp41 介导 HIV-1 与宿主细胞膜的融合，因此 gp41 抑制剂是一种极具吸引力的抗 HIV 药物。我们以前曾报道过一种具有 Y 型结构的高效 HIV-1 融合抑制剂 ADS-J1。在这里，我们发现了一种新化合物 ADS-J21，其 Y 型结构与 ADS-J1 相似，但分子量更低。此外，ADS-J21 在体外对不同的 HIV-1 株表现出有效的抗 HIV-1 活性，包括几种 HIV-1 实验室适应株和不同亚型（A 至 F 支系）和滋养体（X4 或 R5）的原代分离株。机理研究表明，ADS-J21 通过靶向保守氨基酸 Lys35 和 Trp32，阻断了 gp41 六螺旋束 (6-HB) 的形成。这些研究结果表明，ADS-J21 可作为一种新的先导化合物，用于进一步优化小分子融合抑制剂的开发。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊