Department of Heterorganic Chemistry, Centre of Molecular and Macromolecular Studies, Lodz, Poland.
Department of Pharmacy, University of Salerno, Fisciano, Salerno, Italy.
Drug Discov Today. 2018 Feb;23(2):260-271. doi: 10.1016/j.drudis.2017.10.017. Epub 2017 Oct 28.
The major internal component of the HIV virion core is the nucleocapsid protein 7 (NCp7), a small, highly basic protein that is essential for multiple stages of the viral replicative cycle, and whose structure is preserved in all viral strains, including clinical isolates from therapy-experienced patients. This key protein is recognised as a potential target for an effective next-generation antiretroviral therapy, because it could offer the possibility to develop broad-spectrum agents that are less prone to select for resistant strains. Here, we provide a comprehensive overview of the covalent NCp7 inhibitors that have emerged over the past 25 years of drug discovery campaigns, emphasising, where possible, their structure-activity relationships (SARs) and pharmacophoric features.
HIV 病毒核心的主要内部组件是核衣壳蛋白 7（NCp7），这是一种小型、高度碱性的蛋白质，对病毒复制周期的多个阶段都是必不可少的，而且其结构在所有病毒株中都得到了保留，包括来自治疗有经验的患者的临床分离株。这种关键蛋白被认为是一种有效的下一代抗逆转录病毒疗法的潜在靶标，因为它有可能开发出广谱药物，从而降低选择耐药株的可能性。在这里，我们全面概述了在过去 25 年的药物发现活动中出现的共价 NCp7 抑制剂，强调了它们的结构-活性关系（SAR）和药效特征。
