对应于刺突糖蛋白七肽区域的肽对严重急性呼吸综合征冠状病毒进入的抑制作用。

Suppression of SARS-CoV entry by peptides corresponding to heptad regions on spike glycoprotein.

作者信息

Yuan Kehu, Yi Ling, Chen Jian, Qu Xiuxia, Qing Tingting, Rao Xi, Jiang Pengfei, Hu Jianhe, Xiong Zikai, Nie Yuchun, Shi Xuanling, Wang Wei, Ling Chen, Yin Xiaolei, Fan Keqiang, Lai Luhua, Ding Mingxiao, Deng Hongkui

机构信息

Department of Cell Biology and Genetics, College of Life Sciences, Peking University, Beijing 100871, PR China.

出版信息

Biochem Biophys Res Commun. 2004 Jul 2;319(3):746-52. doi: 10.1016/j.bbrc.2004.05.046.

DOI:10.1016/j.bbrc.2004.05.046

PMID:15184046

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7111000/

Abstract

Heptad repeat regions (HR1 and HR2) are highly conserved sequences located in the glycoproteins of enveloped viruses. They form a six-helix bundle structure and are important in the process of virus fusion. Peptides derived from the HR regions of some viruses have been shown to inhibit the entry of these viruses. SARS-CoV was also predicted to have HR1 and HR2 regions in the S2 protein. Based on this prediction, we designed 25 peptides and screened them using a HIV-luc/SARS pseudotyped virus assay. Two peptides, HR1-1 and HR2-18, were identified as potential inhibitors, with EC(50) values of 0.14 and 1.19microM, respectively. The inhibitory effects of these peptides were validated by the wild-type SARS-CoV assay. HR1-1 and HR2-18 can serve as functional probes for dissecting the fusion mechanism of SARS-CoV and also provide the potential of further identifying potent inhibitors for SARS-CoV entry.

摘要

七肽重复区域（HR1和HR2）是包膜病毒糖蛋白中高度保守的序列。它们形成六螺旋束结构，在病毒融合过程中起重要作用。一些病毒HR区域衍生的肽已被证明可抑制这些病毒的进入。严重急性呼吸综合征冠状病毒（SARS-CoV）的S2蛋白中也预测存在HR1和HR2区域。基于这一预测，我们设计了25种肽，并使用HIV-荧光素酶/SARS假型病毒试验对它们进行筛选。两种肽HR1-1和HR2-18被鉴定为潜在抑制剂，其半数有效浓度（EC50）值分别为0.14和1.19微摩尔。这些肽的抑制作用通过野生型SARS-CoV试验得到验证。HR1-1和HR2-18可作为剖析SARS-CoV融合机制的功能探针，也为进一步鉴定SARS-CoV进入的有效抑制剂提供了可能。