A screen for inhibitory peptides of hepatitis C virus identifies a novel entry inhibitor targeting E1 and E2.
A screen for inhibitory peptides of hepatitis C virus identifies a novel entry inhibitor targeting E1 and E2.
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丙型肝炎病毒抑制肽筛选鉴定出一种针对 E1 和 E2 的新型进入抑制剂
DOI：
10.1038/s41598-017-04274-8
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发表时间：
2017-06-21
影响因子：
4.6
通讯作者：
Tan W
中科院分区：
文献类型：
--
作者：
Yin P;Zhang L;Ye F;Deng Y;Lu S;Li YP;Zhang L;Tan W
丙型肝炎病毒（HCV）进入肝细胞是一个多步骤的过程，是一个有前途的抗病毒干预的目标。病毒包膜蛋白E1 E2在HCV进入中起关键作用。在这项研究中，我们试图通过筛选覆盖E1 E2的重叠肽库来鉴定HCV的肽抑制剂。对肽库进行筛选，发现了几种新的抗HCV肽。从糖蛋白E2中选择了四种肽用于进一步研究。每种肽的50%有效剂量（ED 50）约为5 nM。我们的数据表明，这些肽抑制HCV进入后附着步骤。此外，这些肽阻断了HCVDNA的细胞间传播，并对HCVDNA具有广谱的抗病毒作用。当与IFN-α2b或抗CD 81抗体联合时，这些肽表现出对HCV 1感染的联合抑制作用。有趣的是，我们观察到E2-42与E1和E2相关。我们的研究结果表明，E2-42抑制HCV通过E1和E2进入。这些发现为HCV治疗的发展提供了新的途径。
Hepatitis C virus (HCV) entry into hepatocytes is a multistep process that represents a promising target for antiviral intervention. The viral envelope protein E1E2 plays a critical role in HCV entry. In this study, we sought to identify peptide inhibitors of HCV by screening a library of overlapping peptides covering E1E2. Screening the peptide library identified several novel anti-HCV peptides. Four peptides from glycoprotein E2 were selected for further investigation. The 50% effective dose (ED50) was approximately 5 nM for each peptide. Our data indicated that these peptides inhibited HCV entry at the post-attachment step. Moreover, these peptides blocked cell-to-cell transmission of HCVcc and had broad-spectrum antiviral effects on HCVcc. These peptides exhibited combination inhibitory effects on HCVcc infection when combined with IFN-α2b or anti-CD81 antibody. Interestingly, we observed that E2-42 associated with E1 and E2. Our results indicate that E2-42 inhibits HCV entry via E1 and E2. These findings suggest a new avenue for HCV therapeutic development.