Characterizing the anti-HIV activity of papuamide A.
Characterizing the anti-HIV activity of papuamide A.
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DOI：
10.3390/md20080027
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发表时间：
2008
期刊：
影响因子：
5.4
通讯作者：
Barrows LR
中科院分区：
文献类型：
--
作者：
Andjelic CD;Planelles V;Barrows LR
Papuamide A是一类海洋衍生的环状缩酚肽的代表，据报道具有体外抗HIV-1的细胞保护活性。我们在这里表明，papuamide A作为一个进入抑制剂，防止人类免疫缺陷病毒感染的宿主细胞，这种抑制不是特定的R5或X4嗜性病毒。这种对病毒进入的抑制被确定为不是由于papuamide A与CD 4或HIV gp 120结合，这两种蛋白质参与细胞-病毒识别和结合。此外，papuamide A能够抑制表达水泡性口炎病毒或嗜酸性鼠白血病病毒包膜糖蛋白的HIV假型病毒，表明病毒进入抑制机制不是HIV-1包膜糖蛋白特异性的。假型病毒的延时添加研究表明，papuamide A仅在病毒生命周期的初始阶段抑制病毒感染。此外，预处理研究表明，papuamide A的作用靶点是病毒，而不是细胞。总之，这些结果表明papuamide A抑制HIV-1的直接杀病毒机制。我们还证明了其他papuamides（B-D）能够抑制病毒进入，表明2，3-二氨基丁酸残基的游离氨基部分不是杀病毒活性所必需的。
Papuamide A is representative of a class of marine derived cyclic depsipeptides, reported to have cytoprotective activity against HIV-1 in vitro. We show here that papuamide A acts as an entry inhibitor, preventing human immunodeficiency virus infection of host cells and that this inhibition is not specific to R5 or X4 tropic virus. This inhibition of viral entry was determined to not be due to papuamide A binding to CD4 or HIV gp120, the two proteins involved in the cell-virus recognition and binding. Furthermore, papuamide A was able to inhibit HIV pseudotype viruses expressing envelope glycoproteins from vesicular stomatitis virus or amphotropic murine leukemia virus indicating the mechanism of viral entry inhibition is not HIV-1 envelope glycoprotein specific. Time delayed addition studies with the pseudotyped viruses show that papuamide A inhibits viral infection only at the initial stage of the viral life cycle. Additionally, pretreatment studies revealed that the virus, and not the cell, is the target of papuamide A’s action. Together, these results suggest a direct virucidal mechanism of HIV-1 inhibition by papuamide A. We also demonstrate here that the other papuamides (B-D) are able to inhibit viral entry indicating that the free amino moiety of 2,3-diaminobutanoic acid residue is not required for the virucidal activity.
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