A wide range of medium-sized, highly cationic, α-helical peptides show antiviral activity against herpes simplex virus
A wide range of medium-sized, highly cationic, α-helical peptides show antiviral activity against herpes simplex virus
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DOI：
10.1016/j.antiviral.2004.08.003
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发表时间：
2004-11-01
影响因子：
7.6
通讯作者：
Gutteberg, TJ
中科院分区：
文献类型：
--
作者：
Jenssen, H;Andersen, JH;Gutteberg, TJ
合成了10个高阳离子的α -螺旋肽，并测定了它们对单纯疱疹病毒1和2 （HSV-1和HSV-2）的抗病毒活性。其中一些肽被发现具有抗病毒活性。多肽对硫酸肝素（HS）的亲和力随着阳离子残基数量的增加而增加。净电荷可能对抗hsv -1活性起决定性作用，而肽的二级结构似乎对抗hsv -2活性更重要。这些肽能够抑制HSV-1进入宿主细胞，可能是通过阻断细胞表面的HS。当细胞在加入病毒之前暴露于肽时，HSV斑块的形成以紧密依赖的方式被抑制。在加入肽之前，让病毒附着在细胞表面，观察到抑制活性较低。然而，与未经治疗的对照组相比，斑块大小更小，这表明肽也可能干扰病毒的细胞间传播。两种最有效的抗病毒肽显示出与阿昔洛韦对HSV的协同作用。(C) 2004 Elsevier B.V.版权所有
Ten highly cationic, alpha-helical peptides were synthesized and tested for antiviral activity against herpes simplex virus 1 and 2 (HSV-1 and HSV-2). Several of the peptides were found to exhibit antiviral activity. The peptides affinity for heparan sulfate (HS) increased with the number of cationic residues. Net charge could be decisive for the anti-HSV-1 activity, while secondary structure of the peptides seems more important for the anti-HSV-2 activity. The peptides were able to inhibit the entry of HSV-1 into the host cell, probably by blocking HS at the cell surface. HSV plaque formation was inhibited in a close-dependent manner when cells were exposed to the peptides prior to the addition of virus. Lower inhibition activity was observed when the virus was allowed to attach to the cell surface before the addition of peptide. However, the plaque size was smaller compared to the untreated control, indicating that the peptides may also interfere with cell-to-cell spread of the virus. The two most potent antiviral peptides exhibited synergy with acyclovir against HSV. (C) 2004 Elsevier B.V. All rights reserved.