蜂毒肽Protopolybia-MPⅢ及其优化突变体对HSV-1病毒复制周期不同阶段的抑制活性研究  

Inhibitory Activity of Wasp Venom Peptide Protopolybia-MPⅢand Its Optimized Mutants on HSV-1 Replica⁃tion of Different Stages

作　　者：孙芳 邬理莉 覃陈虎 罗旭东 陈宗运 叶祥东[1,2] SUN Fang;WU Li-li;QIN Chen-hu;LUO Xu-dong;CHEN Zong-yun;YE Xiang-dong(Department of Biochemistry and Molecular Biology,College of Basic Medical Sciences;Hubei Key Labo-ratory of Wudang Local Chinese Medicine Research,Hubei University of Medicine,Shiyan,Hubei 442000,China)

机构地区：[1]湖北医药学院基础医学院生物化学教研室 [2]湖北医药学院武当特色中药研究湖北省重点实验室,湖北十堰442000

出　　处：《湖北医药学院学报》2024年第4期343-348,共6页Journal of Hubei University of Medicine

基　　金：国家自然科学基金青年项目(82204407);湖北省科技厅自然科学基金项目(2023AFB296);湖北医药学院青年学者培养项目(2021QDJZR019)。

摘　　要：目的:研究蜂毒肽Protopolybia-MPⅢ及其优化突变体MPⅢ-3/4/7/10/14在体外对Ⅰ型单纯疱疹病毒(HSV-1)复制周期不同阶段的抑制活性。方法:通过qPCR技术和多肽分阶段孵育平台,检测蜂毒肽Protopoly⁃bia-MPⅢ及5个优化突变体在Vero细胞内对HSV-1感染的预防作用,以及其对HSV-1复制周期不同阶段的影响。结果:Protopolybia-MPⅢ多肽突变体MPⅢ-4/10/14预处理Vero细胞后去除上清,能限制HSV-1感染。进一步通过多肽抗病毒作用阶段分析实验,发现野生型多肽Protopolybia-MPⅢ主要作用于HSV-1复制周期的吸附阶段,而MPⅢ-3/14主要作用于病毒复制周期的进入/融合以及进入后阶段,MPⅢ-4/7主要作用于病毒复制周期的吸附以及进入/融合阶段,MPⅢ-10主要作用于病毒复制周期的吸附以及进入后阶段。结论:本工作明确了蜂毒肽Protopolybia-MPⅢ及其突变体MPⅢ-3/4/7/10/14对HSV-1复制周期不同阶段的抑制活性,初步阐明了Protopolybia-MPⅢ多肽优化突变体抗病毒活性提高的原因,为胡蜂抗病毒多肽的分子设计和药用研究奠定基础。Objective To study the inhibitory activity of the wasp venom peptide Protopolybia-MPⅢand its optimized mu⁃tants MPⅢ-3/4/7/10/14 on different stages of herpes simplex virus-1(HSV-1)replication in vitro.Methods The pre⁃ventive effects of Protopolybia-MPⅢand its five optimized mutants on HSV-1 infection in Vero cells,as well as their effects on different stages of HSV-1 replication,were detected using qPCR and a peptide incubation platform.Results The MPⅢ-4/10/14 limited HSV-1 infection after the removal of the supernatant in preincubated Vero cells.Further analysis of the stages of antiviral activity of the peptides showed that the wild-type peptide Protopolybia-MPⅢmainly acted on the attachment of HSV-1 replication;MPⅢ-3/14 mainly on the entry/fusion and post entry of the virus replication cycle;MPⅢ-4/7 mainly acted on the attachment and entry/fusion stages;MPⅢ-10 mainly on the attachment and entry stages.Conclusion This paper determined the inhibitory activity of Protopolybia-MPⅢand its mutants MPⅢ-3/4/7/10/14 on different stages of HSV-1 replication and preliminarily clarified the reasons for the improved antiviral activity of optimized mutants of Protopolybia-MPⅢ.This study laid the foundation for the molecular design and medicinal research of wasp an⁃tiviral peptides.

关 键 词：胡蜂毒液多肽 优化突变体 Ⅰ型单纯疱疹病毒 复制周期 

分 类 号：R91[医药卫生—药学] R96