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Rational design of novel HIV-1 entry inhibitors by RANTES engineering.

机译:通过RANTES工程合理设计新型HIV-1进入抑制剂。

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摘要

The discovery that the CC chemokines RANTES, MIP-1alpha and MIP-1beta act as potent natural inhibitors of HIV-1, the causative agent of AIDS, and the subsequent identification of CCR5 as a major virus coreceptor have triggered a wealth of basic and applied research approaches aimed at developing safe and effective viral entry inhibitors. Some of these efforts have focused on RANTES engineering with the goal of enhancing the antiviral activity of the native molecule while reducing or abrogating its inflammatory properties. The wavefront generated a decade ago is still on its course, with a flow of promising leads constantly emerging and being evaluated in preclinical studies. Here, we present an overview of this rapidly evolving field, highlighting the most important features of RANTES molecular architecture and structure-function relationships.
机译:CC趋化因子RANTES,MIP-1alpha和MIP-1beta可作为有效的HIV-1天然抑制剂,AIDS的致病因子以及随后将CCR5鉴定为主要病毒共受体的发现引发了许多基础研究和应用旨在开发安全有效的病毒进入抑制剂的研究方法。这些努力中的一些已经集中在RANTES工程上,目的是增强天然分子的抗病毒活性,同时减少或消除其炎症特性。十年前产生的波阵面仍在继续,有希望的线索不断涌现并在临床前研究中得到评估。在这里,我们概述了这个快速发展的领域,重点介绍了RANTES分子结构和结构-功能关系的最重要特征。

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