基靶向HIV-1整合酶的ST抑制剂综述

Targeting HIV-1 integrase with strand transfer inhibitors

Li, Y.; Xuan, S.; Feng, Y.; Yan, A.*

Drug Discovery Today, 2015, 20 (4), 435-449.

    HIV-1整合酶 (IN) 是一种逆转录酶，是HIV病毒将遗传物质整合到宿主细胞的DNA中所必需的酶，因此是病毒复制所必需的酶。在人体中缺乏一种类似的酶，这使HIV-1整合酶成为抗艾滋病病毒药物的一个有趣的靶标。本文简要综述了HIV-1的结构和功能特性。我们基于HIV-1整合酶ST抑制剂 (INSTIs) 的创新化学骨架，分析了已上市的药物、临床候选药物和综合先导化合物库的结合模式。我们使用聚类分析计算方法来识别与生物活性相关的结构特征。从生物和化学信息分析的角度，我们提供了有关HIV-1整合酶ST抑制剂的结构-活性关系的新见解，并阐述了设计创新抑制剂的新策略。

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    HIV-1 integrase (IN) is a retroviral enzyme essential for integration of genetic material into the DNA of the host cell and hence for viral replication. The absence of an equivalent enzyme in humans makes IN an interesting target for anti-HIV drug design. This review briefly overviews the structural and functional properties of HIV-1 IN. We analyze the binding modes of the established drugs, clinical candidates and a comprehensive library of leads based on innovative chemical scaffolds of HIV-1 IN strand transfer inhibitors (INSTIs). Computational clustering techniques are applied for identifying structural features relating to bioactivity. From bio- and chemo-informatics analyses, we provide novel insights into structure–activity relationships of INSTIs and elaborate new strategies for design of innovative inhibitors.

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