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Vaccine. 2008 Jun 6;26(24):3008-15. doi: 10.1016/j.vaccine.2007.12.023. Epub 2008 Jan 10.

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

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Department of Biological and Technological Research, San Raffaele Scientific Institute, Via Olgettina n. 58, 20132 Milan, Italy.


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.

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