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从蝙蝠冠状病毒 HKU4 的刺突蛋白 HR2 结构域中鉴定出有效的 MERS-CoV 融合抑制肽。

Potent MERS-CoV Fusion Inhibitory Peptides Identified from HR2 Domain in Spike Protein of Bat Coronavirus HKU4.

机构信息

Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China.

State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.

出版信息

Viruses. 2019 Jan 14;11(1):56. doi: 10.3390/v11010056.

DOI:10.3390/v11010056
PMID:30646495
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6357153/
Abstract

The Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 and caused continual outbreaks worldwide with high mortality. However, no effective anti-MERS-CoV drug is currently available. Recently, numerous evolutionary studies have suggested that MERS-CoV originated from bat coronavirus (BatCoV). We herein reported that three peptides derived from the HR2 region in spike protein of BatCoV HKU4, including HKU4-HR2P1, HKU4-HR2P2 and HKU4-HR2P3, could bind the MERS-CoV HR1-derived peptide to form a six-helix bundle (6-HB) with high stability. Moreover, these peptides, particularly HKU4-HR2P2 and HKU4-HR2P3, exhibited potent inhibitory activity against MERS-CoV S-mediated cell⁻cell fusion and viral infection, suggesting that these HKU4 HR2-derived peptides could be candidates for futher development as antiviral agents against MERS-CoV infection.

摘要

中东呼吸综合征冠状病毒(MERS-CoV)于 2012 年出现,在全球范围内持续爆发,死亡率很高。然而,目前尚无有效的抗 MERS-CoV 药物。最近,许多进化研究表明,MERS-CoV 起源于蝙蝠冠状病毒(BatCoV)。我们在此报告,来自 BatCoV HKU4 刺突蛋白 HR2 区的三个肽,包括 HKU4-HR2P1、HKU4-HR2P2 和 HKU4-HR2P3,能够结合 MERS-CoV HR1 衍生肽形成具有高稳定性的六螺旋束(6-HB)。此外,这些肽,特别是 HKU4-HR2P2 和 HKU4-HR2P3,对 MERS-CoV S 介导的细胞融合和病毒感染具有很强的抑制活性,表明这些源自 HKU4 HR2 的肽可能是进一步开发抗 MERS-CoV 感染的抗病毒药物的候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb8f/6357153/9cc21c8e3a8a/viruses-11-00056-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb8f/6357153/e8b6c8a8c552/viruses-11-00056-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb8f/6357153/6fd704ca94c9/viruses-11-00056-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb8f/6357153/925ab03fe749/viruses-11-00056-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb8f/6357153/c4f1ed6bb8b8/viruses-11-00056-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb8f/6357153/9cc21c8e3a8a/viruses-11-00056-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb8f/6357153/e8b6c8a8c552/viruses-11-00056-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb8f/6357153/6fd704ca94c9/viruses-11-00056-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb8f/6357153/925ab03fe749/viruses-11-00056-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb8f/6357153/c4f1ed6bb8b8/viruses-11-00056-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb8f/6357153/9cc21c8e3a8a/viruses-11-00056-g005.jpg

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