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 是针对 gp41 的新型 HIV-1 进入抑制剂","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":5.8000,"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":"{\"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\":5.8000,\"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\":\"2024/7/9 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"MICROBIOLOGY\",\"Score\":null,\"Total\":0}","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":"2024/7/9 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
ADS-J21 is a novel HIV-1 entry inhibitor targeting gp41
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.
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