MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, 102206, China.
Sci Rep. 2017 Jun 21;7(1):3976. doi: 10.1038/s41598-017-04274-8.
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.
丙型肝炎病毒 (HCV) 进入肝细胞是一个多步骤的过程，代表了抗病毒干预的一个有前途的靶点。病毒包膜蛋白 E1E2 在 HCV 进入中起着关键作用。在这项研究中，我们通过筛选覆盖 E1E2 的重叠肽文库，试图鉴定 HCV 的肽抑制剂。筛选肽文库鉴定出了几种新型抗 HCV 肽。从糖蛋白 E2 中选择了四个肽进行进一步研究。每个肽的 50%有效剂量 (ED50) 约为 5 nM。我们的数据表明，这些肽在附着后步骤抑制 HCV 进入。此外，这些肽阻断了 HCVcc 的细胞间传播，并对 HCVcc 具有广谱抗病毒作用。当与 IFN-α2b 或抗 CD81 抗体联合使用时，这些肽对 HCVcc 感染表现出联合抑制作用。有趣的是，我们观察到 E2-42 与 E1 和 E2 相关。我们的结果表明，E2-42 通过 E1 和 E2 抑制 HCV 进入。这些发现为 HCV 治疗的发展提供了一个新途径。
