Potent HIV fusion inhibitors against Enfuvirtide-resistant HIV-1 strains
Potent HIV fusion inhibitors against Enfuvirtide-resistant HIV-1 strains
复制标题
针对恩夫韦肽耐药 HIV-1 菌株的有效 HIV 融合抑制剂
DOI：
10.1073/pnas.0807335105
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发表时间：
2008-10-21
影响因子：
11.1
通讯作者：
Dai, Qiuyun
中科院分区：
文献类型：
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作者：
He, Yuxian;Cheng, Jianwei;Dai, Qiuyun
T20(通用名称：enfuvirtie，商标：Fuzeon)是FDA批准的唯一一种用于治疗对当前抗逆转录病毒药物无效的艾滋病毒/艾滋病患者的艾滋病毒融合抑制剂。然而，它在体外和体内都会迅速诱导耐药。在前人抗HIV多肽结构和功能信息的基础上，我们设计了一种名为CP32M的HIV融合抑制物，它是一种32聚体合成肽，可以高效地抑制多种R5或R5X4表型的HIV-1原代分离株的感染，包括对T20和C34(另一种抗HIV多肽)具有抗性的O组病毒(BCF02)。引人注目的是，CP32M对一组对T20和C34高度耐药的HIV-1突变株的感染具有特别的效力(在低皮摩尔水平)。这些发现表明，CP32M可以进一步开发为对抗多药耐药HIV-1的抗病毒疗法。
T20 (generic name: Enfuvirtide, brand name: Fuzeon) is the only FDA-approved HIV fusion inhibitor that is being used for treatment of HIV/AIDS patients who have failed to respond to current antiretroviral drugs. However, it rapidly induces drug resistance in vitro and in vivo. On the basis of the structural and functional information of anti-HIV peptides from a previous study, we designed an HIV fusion inhibitor named CP32M, a 32-mer synthetic peptide that is highly effective in inhibiting infection by a wide range of primary HIV-1 isolates from multiple genotypes with R5- or dual-tropic (R5X4) phenotype, including a group O virus (BCF02) that is resistant to T20 and C34 (another anti-HIV peptide). Strikingly, CP32M is exceptionally potent (at low picomolar level) against infection by a panel of HIV-1 mutants highly resistant to T20 and C34. These findings suggest that CP32M can be further developed as an antiviral therapeutic against multidrug resistant HIV-1.