Trilobatin as an HIV-1 entry inhibitor targeting the HIV-1 Gp41 envelope
Trilobatin as an HIV-1 entry inhibitor targeting the HIV-1 Gp41 envelope
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Trilobatin 作为 HIV-1 进入抑制剂，靶向 HIV-1 Gp41 包膜
DOI：
10.1002/1873-3468.13113
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发表时间：
2018
期刊：
影响因子：
3.5
通讯作者：
Li Lin
中科院分区：
文献类型：
--
作者：
Yin Shuwen;Zhang Xuanxuan;Lai Fangyuan;Liang Taizhen;Wen Jiayong;Lin Wanying;Qiu Jiayin;Liu Shuwen;Li Lin
HIV-1跨膜蛋白gp 41通过在HIV进入过程中形成稳定的六螺旋束发挥关键作用。由于gp 41的高度保守序列，开发有效且安全的靶向gp 41的小分子化合物是一个很好的选择。目前，具有抗HIV活性的天然聚阴离子成分引起了人们的关注。在这里，我们首次发现糖基化的二氢查耳酮，三叶苷，在体外表现出广泛的抗HIV-1活性和低细胞毒性。定点突变分析表明，位于gp 41口袋形成位点的疏水残基（I564）是三叶苷抗HIV活性的关键。此外，三叶苷与其他抗逆转录病毒药物联合显示出协同抗HIV活性。Trilobatin具有良好的潜力，可开发为临床联合治疗的小分子HIV-1进入抑制剂。
HIV‐1 transmembrane protein gp41 plays a crucial role by forming a stable six‐helix bundle during HIV entry. Due to highly conserved sequence of gp41, the development of an effective and safe small‐molecule compound targeting gp41 is a good choice. Currently, natural polyanionic ingredients with anti‐HIV activities have aroused concern. Here, we first discovered that a glycosylated dihydrochalcone, trilobatin, exhibited broad anti‐HIV‐1 activity and low cytotoxicityin vitro. Site‐directed mutagenesis analysis suggested that the hydrophobic residue (I564) located in gp41 pocket‐forming site is pivotal for anti‐HIV activity of trilobatin. Furthermore, trilobatin displayed synergistic anti‐HIV activities combined with other antiretroviral agents. Trilobatin has a good potential to be developed as a small‐molecule HIV‐1 entry inhibitor for clinical combination therapy.