Anti-HIV Drug Discovery and Development: Current Innovations and Future Trends
Anti-HIV Drug Discovery and Development: Current Innovations and Future Trends
复制标题
抗艾滋病毒药物的发现和开发：当前创新和未来趋势
DOI：
10.1021/acs.jmedchem.5b00497
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发表时间：
2016-04-14
影响因子：
7.3
通讯作者：
Liu, Xinyong
中科院分区：
文献类型：
--
作者：
Zhan, Peng;Pannecouque, Christophe;Liu, Xinyong
联合抗逆转录病毒疗法(CART)治疗HIV感染的早期有效性已经受到HIV多药耐药株的快速发展、生物利用度差和累积毒性的一定程度的影响，因此需要寻找新的抗逆转录病毒药物发现的替代策略和具有新的作用模式或靶点的额外治疗药物。从这个角度，我们首先回顾了当前抗逆转录病毒药物发现和优化的策略，并从最近的文献中选择了一些例子。我们重点介绍了以磷酸酯为基础的前药的发展，作为一种改善HIV抑制剂水溶解的手段，以及底物包膜假说的引入，作为克服HIV耐药性的新方法。最后，我们讨论了未来的研究方向，包括开发新的抗逆转录病毒靶标的机会，以及激活潜伏的艾滋病毒储存库作为根除病毒的手段的战略。
The early effectiveness of combinatorial antiretroviral therapy (CART) in the treatment of HIV infection has been compromised to some extent by rapid development of multidrug-resistant HIV strains, poor bioavailability, and cumulative toxicities, and so there is a need for alternative strategies of antiretroviral drug discovery and additional therapeutic agents with novel action modes or targets. From this perspective, we first review current strategies of antiretroviral drug discovery and optimization, with the aid of selected examples from the recent literature. We highlight the development of phosphate ester-based prodrugs as a means to improve the aqueous solubility of HIV inhibitors, and the introduction of the substrate envelope hypothesis as a new approach for overcoming HIV drug resistance. Finally, we discuss future directions for research, including opportunities for exploitation of novel antiretroviral targets, and the strategy of activation of latent HIV reservoirs as a means to eradicate the virus.