Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, 250012, Jinan, Shandong, China.
Centro de Biologia Molecular "Severo Ochoa" (Consejo Superior de Investigaciones Científicas & Universidad Autonoma de Madrid), Madrid, Spain.
Curr Med Chem. 2018;25(14):1682-1702. doi: 10.2174/0929867324666170113110839.
Combinations of antiretroviral drugs are successfully used to treat HIV-infected patients. However, drug resistance is a major problem that makes discovery of new antiretroviral drugs an ongoing priority. The ribonuclease H (RNase H) activity of the HIV-1 reverse transcriptase catalyzes the selective hydrolysis of the RNA strand of RNA:DNA heteroduplex replication intermediates, and represents an attractive unexploited target for drug development. This review reports on recent progress in the characterization of HIV-1 RNase H inhibitors from 2013 to 2016, describing their chemical structures, structureactivity relationship and binding modes. Focus is given to emerging medicinal chemistry principles and insights into the discovery and development of RNase H inhibitors.
抗逆转录病毒药物的联合使用已成功地用于治疗 HIV 感染患者。然而，耐药性是一个主要问题，这使得发现新的抗逆转录病毒药物成为一个持续的优先事项。HIV-1 逆转录酶的核糖核酸酶 H（RNase H）活性催化 RNA:DNA 杂合复制中间体的 RNA 链的选择性水解，代表了药物开发中一个有吸引力但尚未开发的目标。本综述报告了 2013 年至 2016 年 HIV-1 RNase H 抑制剂的最新研究进展，描述了它们的化学结构、结构-活性关系和结合模式。重点介绍了 RNase H 抑制剂发现和开发的新兴药物化学原理和见解。
