Opening the HIV envelope: potential of CD4 mimics as multifunctional HIV entry inhibitors.
Opening the HIV envelope: potential of CD4 mimics as multifunctional HIV entry inhibitors.
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DOI：
10.1097/coh.0000000000000637
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发表时间：
2020-09
影响因子：
4.1
通讯作者：
Finzi A
中科院分区：
文献类型：
--
作者：
Laumaea A;Smith AB 3rd;Sodroski J;Finzi A
全球每年有近200万人感染人类免疫缺陷病毒(HIV-1)，略高于三分之二的人将能够获得延长生命的抗病毒药物。然而，抗药性的快速发展带来了挑战，因此，产生更有效的治疗方法不仅是必要的，而且是必要的努力。这篇综述讨论了一组HIV-1进入抑制剂，被称为CD4模拟物，它们利用了HIV-1包膜糖蛋白(Env)和受体CD4之间的高度保守的关系。我们综述了这些抑制剂的结构/功能指导的进化，支持广泛和有效的功能拮抗的重要机制，在动物和生理相关的体外模型中显示的最新实用证据，以及有效的新一代抑制剂的最新进展。这篇综述突出了CD_4模拟分子作为多功能治疗药物的潜力。
Close to two million individuals globally become infected with human immunodeficiency virus (HIV-1) each year and just over two thirds will have access to life-prolonging antivirals. However, the rapid development of drug resistance creates challenges, such that generation of more effective therapies is not only warranted but a necessary endeavour. This review discusses a group of HIV-1 entry inhibitors known as CD4 mimics which exploit the highly conserved relationship between the HIV-1 envelope glycoprotein (Env) and the receptor, CD4. We review the structure/function guided evolution of these inhibitors, vital mechanistic insights that underpin broad and potent functional antagonism, recent evidence of utility demonstrated in animal and physiologically relevant in vitro models, and current progress towards effective new-generation inhibitors. This review highlights the promising potential of CD4 mimetics as multifunctional therapeutics.