1. ADS-J21 is a novel HIV-1 entry inhibitor targeting gp41
- Author
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Ruiying Liang, Dou Dou, Chunying Wang, Shanshan Huo, Yang Wu, Juan Wang, Zhengsen Yu, Shuomin Zhang, Jingjing Xu, Yue Liu, Peng Liu, Shibo Jiang, and Fei Yu
- Subjects
HIV-1 ,gp41 ,Small molecule ,Inhibitors ,Broad-spectrum ,Microbiology ,QR1-502 ,Genetics ,QH426-470 - 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.
- Published
- 2024
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