打开 HIV 信封：CD4 模拟物作为多功能 HIV 进入抑制剂的潜力。
Opening the HIV envelope: potential of CD4 mimics as multifunctional HIV entry inhibitors.
机构信息
Centre de Recherche du CHUM.
Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec, Canada.
出版信息
Curr Opin HIV AIDS. 2020 Sep;15(5):300-308. doi: 10.1097/COH.0000000000000637.
Abstract
PURPOSE OF REVIEW
Close to 2 million individuals globally become infected with 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 and the receptor, CD4.
RECENT FINDINGS
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.
SUMMARY
The current review highlights the promising potential of CD4 mimetics as multifunctional therapeutics.
摘要
目的综述
全球每年有近 200 万人感染 HIV-1，其中只有超过三分之二的人能够获得延长生命的抗病毒药物。然而，耐药性的迅速发展带来了挑战，因此不仅需要而且有必要开发更有效的治疗方法。本综述讨论了一组被称为 CD4 模拟物的 HIV-1 进入抑制剂，这些抑制剂利用了 HIV-1 包膜糖蛋白和受体 CD4 之间高度保守的关系。
最新发现
我们综述了这些抑制剂的结构/功能引导进化，这些重要的机制见解为广泛而有效的功能拮抗提供了基础，近期在动物和生理相关的体外模型中证明了其有效性的证据，以及朝着有效新一代抑制剂的当前进展。
总结
本综述强调了 CD4 模拟物作为多功能治疗药物的有前途的潜力。
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