The entry of entry inhibitors: A fusion of science and medicine
The entry of entry inhibitors: A fusion of science and medicine
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DOI：
10.1073/pnas.1932511100
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发表时间：
2003-09-16
影响因子：
11.1
通讯作者：
Doms, RW
中科院分区：
文献类型：
--
作者：
Moore, JP;Doms, RW
HIV-1要进入细胞，其包膜蛋白（Env）必须顺序地与CD4和趋化因子辅助受体结合，触发Env的构象变化，最终导致病毒和宿主细胞膜融合。病毒进入途径的每一步都是称为进入抑制剂的新型抗病毒药物的潜在靶标。越来越多的进入抑制剂正在临床开发中，其中一种已经获得美国食品和药物管理局的许可。随着对现有逆转录酶和蛋白酶抑制剂具有很大抗性的病毒株的出现，进入抑制剂的开发恰逢其时。尽管如此，由于所有的进入抑制剂都以某种方式靶向HIV-1的高度可变的Env蛋白，因此这类药物在有效应用方面可能面临挑战。Env密度、受体表达水平、亲和力和受体呈递的差异都是影响这类有前景的新型抗病毒药物临床反应的因素。
For HIV-1 to enter a cell, its envelope protein (Env) must sequentially engage CD4 and a chemokine coreceptor, triggering conformational changes in Env that ultimately lead to fusion between the viral and host cell membranes. Each step of the virus entry pathway is a potential target for novel antiviral agents termed entry inhibitors. A growing number of entry inhibitors are under clinical development, with one having already been licensed by the Food and Drug Administration. With the emergence of virus strains that are largely resistant to existing reverse transcriptase and protease inhibitors, the development of entry inhibitors comes at an opportune time. Nonetheless, because all entry inhibitors target in some manner the highly variable Env protein of HIV-1, there are likely to be challenges in their efficient application that are unique to this class of drugs. Env density, receptor expression levels, and differences in affinity and receptor presentation are all factors that could influence the clinical response to this promising class of new antiviral agents.