The Medical College of Nanchang University, Nanchang, Jiangxi, China.
Department of Gynecology and Obstetrics, The First Affiliated Hospital of Nanchang University, University. Nanchang, Jiangxi, China.
AIDS Rev. 2020 Oct 26;22(4):221-226. doi: 10.24875/AIDSRev.20000050.
HIV-1 infection poses a major threat to the public health worldwide. The antiretroviral agents that are currently used to treat HIV-1 infection target viral reverse transcriptase, integrase and protease, or block the fusion of viral envelop and cell membrane. Studies have shown that the HIV-1 encoded protein Nef plays an important role in the pathogenesis of viral infection. Nef ensures efficient counterattack against host immune responses as well as long-term evasion of immune surveillance. In addition, Nef, expressing at a high level early in the viral life cycle, is required for maintaining a high viral load in the persistent infection in vivo and for full pathologic potential. Therefore, Nef may be an excellent target to treat HIV-1 infection. In this manuscript, we reviewed five potential Nef inhibitors, namely, DLC27-14, t ightly bound hydroxypyrazole HIV-1 Nef inhibitor B9, 2c-like inhibitors, N-(3-aminoquinoxalin-2-yl)-4-chlorobenzenesulfonamide and compound 1[(7-oxo-7H-benzo[anthracene]-3-yl)amino]anthraquinone, and their working mechanisms. These drugs may be further developed into new regimens for the treatment of HIV-1 infection.
HIV-1 感染对全球公共卫生构成重大威胁。目前用于治疗 HIV-1 感染的抗逆转录病毒药物靶向病毒逆转录酶、整合酶和蛋白酶,或阻断病毒包膜与细胞膜的融合。研究表明,HIV-1 编码的蛋白 Nef 在病毒感染的发病机制中起着重要作用。Nef 确保了对宿主免疫反应的有效反击,以及对免疫监视的长期逃避。此外,Nef 在病毒生命周期的早期高水平表达,对于维持体内持续性感染中的高病毒载量和充分的病理潜能是必需的。因此,Nef 可能是治疗 HIV-1 感染的一个很好的靶点。在这篇手稿中,我们综述了五种潜在的 Nef 抑制剂,即 DLC27-14、紧密结合的羟吡唑 HIV-1 Nef 抑制剂 B9、2c 样抑制剂、N-(3-氨基喹喔啉-2-基)-4-氯苯磺酰胺和化合物 1[(7-氧代-7H-苯并[蒽]-3-基)氨基]蒽醌,及其作用机制。这些药物可能进一步开发成治疗 HIV-1 感染的新方案。