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Review Article

针对 HIV-1 整合酶和逆转录酶相关核糖核酸酶 H 的计算机辅助抗病毒药物设计的最新进展

卷 29, 期 10, 2022

发表于: 08 July, 2021

页: [1664 - 1676] 页: 13

弟呕挨: 10.2174/0929867328666210708090123

价格: $65

摘要

获得性免疫缺陷综合征 (AIDS) 长期以来一直是一种威胁生命的慢性疾病。虽然，广泛的抗逆转录病毒药物方案适用于成功抑制人类免疫缺陷病毒 1 型 (HIV-1) 感染者的病毒复制。艾滋病治疗过程中突变引起的耐药问题迫使人们不断寻找新的抗病毒药物。 HIV-1 整合酶 (IN) 和逆转录酶相关核糖核酸酶 (RT-RNase H) 是 HIV-1 复制过程中的两种关键酶，已成为设计新型 HIV-1 抗病毒药物的可药化靶点。在 HIV-1 IN 和/或 RT-RNase H 抑制剂的开发过程中，计算机辅助药物设计 (CADD)，包括同源性建模、药效团、对接、分子动力学 (MD) 模拟和结合自由能计算，是一个重要的工具加速新候选药物的发现并降低抗病毒药物开发的成本。在这篇综述中，我们总结了针对 HIV-1 IN 或/和 RT-RNase H 的单靶点和双靶点抑制剂设计的最新进展，以及基于计算方法预测突变诱导的耐药性。我们重点介绍了已报道文献的结果，并对未来设计新型和更有效的抗病毒药物提出了一些看法。

关键词: HIV-1整合酶、逆转录酶相关核糖核酸酶H、计算机辅助药物设计、耐药性预测、分子动力学、抗病毒药物。

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