Chemokine antagonists as therapeutics: Focus on HIV-1

被引：59

作者：

Tsibris, Athe M. N.

Kuritzkes, Daniel R.

机构：

[1] Harvard Univ, Sch Med, Div Aids, Boston, MA 02115 USA

[2] Brigham & Womens Hosp, Sect Retroviral Therapeut, Boston, MA 02115 USA

来源：

ANNUAL REVIEW OF MEDICINE | 2007年 / 58卷

关键词：

virus entry; CCR5; CXCR4; viral tropism; G protein-coupled receptors;

D O I：

10.1146/annurev.med.58.080105.102908

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Human immunodeficiency virus type 1 (HIV-1) entry into target cells is a multistep process involving the interaction of viral envelope proteins with cell surface receptors. Binding to CD4 is followed by engagement of specific chemokine receptors (CCR5 or CXCR4), triggering molecular rearrangements in the envelope transmembrane subunit that result in membrane fusion. Chemokine receptor antagonists that block the interaction of the HIV-1 envelope with CCR5 or CXCR4 potently inhibit HIV-1 in vitro. Pilot studies of orally bioavailable small-molecule CCR5 inhibitors in HIV-1-infected subjects have provided proof of concept for this novel drug class; phase III safety and efficacy trials are under way.

引用

收藏

页码：445 / 459

页数：15

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