Identification of a peptide derived from the heptad repeat 2 region of the porcine epidemic diarrhea virus (PEDV) spike glycoprotein that is capable of suppressing PEDV entry and inducing neutralizing antibodies.

Identification of a peptide derived from the heptad repeat 2 region of the porcine epidemic diarrhea virus (PEDV) spike glycoprotein that is capable of suppressing PEDV entry and inducing neutralizing antibodies.
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鉴定源自猪流行性腹泻病毒 (PEDV) 刺突糖蛋白七肽重复 2 区域的肽,该肽能够抑制 PEDV 进入并诱导中和抗体

DOI:
10.1016/j.antiviral.2017.11.021
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发表时间:
2018-03
期刊:
影响因子:
7.6
通讯作者:
Huang YW
Huang YW
中科院分区:
医学2区
文献类型:
--
作者:
Zhao P;Wang B;Ji CM;Cong X;Wang M;Huang YW

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七肽重复序列(HR)区域是位于包膜病毒糖蛋白中的高度保守基序,可形成六螺旋束结构,在病毒融合过程中至关重要。研究表明,一些病毒HR区域衍生的肽能够抑制病毒入侵。预测猪流行性腹泻病毒(PEDV)的刺突糖蛋白S2亚基中存在HR区域(HR1和HR2)。基于此分析,选取了6种源自HR1和HR2的肽,在大肠杆菌中表达、纯化并进行特性分析。在PEDV体外感染试验中,3种肽(HR2M、HR2L和HR2P)被鉴定为潜在的竞争性抑制剂,其中HR2P肽的抑制作用最强。进一步研究表明,用HR2P肽免疫小鼠可诱导产生能在体外中和PEDV感染的抗体。这些结果表明,HR2P肽和抗HR2P抗体可作为解析PEDV融合机制的工具,为寻找具有治疗价值的抗PEDV感染强效抑制剂提供指导。 表达并分析了6种源自PEDV S糖蛋白七肽重复序列(HR)1和2区域的肽。 3种肽(HR2M、HR2L和HR2P)在体外表现出抗病毒活性。 用HR2P肽免疫小鼠诱导产生的抗体能在体外中和PEDV感染。 HR2P肽可作为一种潜在的抗PEDV感染抗病毒药物。
Heptad repeat (HR) regions are highly conserved motifs located in the glycoproteins of enveloped viruses that form a six-helix bundle structure and is important in the process of virus fusion. Peptides derived from the HR regions of some viruses have also been shown to inhibit viral entry. Porcine epidemic diarrhea virus (PEDV) was predicted to have HR regions (HR1 and HR2) in the spike glycoprotein S2 subunit. Based on this analysis, six peptides derived from HR1 and HR2 were selected, expressed in Escherichia coli, purified, and characterized. Three peptides (HR2M, HR2L and HR2P) were identified as potential competitive inhibitors in PEDV in vitro infection assays, with the HR2P peptide representing the most potent inhibitor. Further study indicated that immunization of HR2P in mice elicited antibodies capable of neutralizing PEDV infection in vitro. These results demonstrate that the HR2P peptide and anti-HR2P antibody can serve as a tool for dissecting the fusion mechanism of PEDV, guiding the search for potent inhibitors with therapeutic value against PEDV infection. Six peptides derived from heptad repeat (HR) 1 and 2 regions of PEDV S glycoprotein were expressed and characterized. Three peptides (HR2M, HR2L and HR2P) exhibited antiviral activity in vitro. Immunization of the HR2P peptide in mice elicited antibodies capable of neutralizing PEDV infection in vitro. HR2P peptide can serve as a potential antiviral drug against PEDV infection.
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