Direct inactivation of human immunodeficiency virus type 1 by a novel small-molecule entry inhibitor, DCM205
Direct inactivation of human immunodeficiency virus type 1 by a novel small-molecule entry inhibitor, DCM205
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DOI：
10.1128/aac.01001-06
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发表时间：
2007-05-01
影响因子：
4.9
通讯作者：
North, Thomas W.
中科院分区：
文献类型：
--
作者：
Duong, Yen T.;Meadows, D. Christopher;North, Thomas W.
由于有4000多万人携带人类免疫缺陷病毒(HIV)，迫切需要开发能够以局部杀微生物剂的形式使用的药物，以防止通过性传播感染。DCM205是最近发现的一种I型艾滋病毒(HIV-1)小分子抑制剂，能够在没有细胞靶点的情况下直接灭活HIV-1。DCM205对CXCR4、CCR5和双嗜性HIV-1实验室适应株和主要毒株具有活性。DCM205与HIV-1包膜糖蛋白结合，竞争研究绘制了DCM205与gp120的V3环或附近的结合图。与这个位点的结合干扰了可溶性的CD4相互作用。DCM205具有使病毒颗粒失效的能力，是一种很有前途的新型HIV进入抑制剂，可作为预防HIV-1/AIDS的策略。
With more than 40 million people living with human immunodeficiency virus (HIV), there is an urgent need to develop drugs that can be used in the form of a topical microbicide to prevent infection through sexual transmission. DCM205 is a recently discovered small-molecule inhibitor of HIV type I (HIV-1) that is able to directly inactivate HIV-1 in the absence of a cellular target. DCM205 is active against CXCR4-, CCR5-, and dual-tropic laboratory-adapted and primary strains of HIV-1. DCM205 binds to the HIV-1 envelope glycoprotein, and competition studies map the DCM205 binding at or near the V3 loop of gp120. Binding to this site interferes with the soluble CD4 interaction. With its ability to disable the virus particle, DCM205 represents a promising new class of HIV entry inhibitor that can be used as a strategy in the prevention of HIV-1/AIDS.