蜂毒肽Protopolybia-MP Ⅲ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-MP Ⅲ and Its Optimized Mutants on HSV-1 Replica-tion of Different Stages
孙芳 1邬理莉 2覃陈虎 1罗旭东 1陈宗运 1叶祥东1
作者信息
- 1. 湖北医药学院基础医学院生物化学教研室;武当特色中药研究湖北省重点实验室,湖北 十堰 442000
- 2. 湖北医药学院基础医学院生物化学教研室
- 折叠
摘要
目的:研究蜂毒肽Protopolybia-MP Ⅲ及其优化突变体MP Ⅲ-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-MP Ⅲ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-MP Ⅲ多肽突变体MP Ⅲ-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-MP Ⅲ主要作用于HSV-1 复制周期的吸附阶段,而MP Ⅲ-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,MP Ⅲ-4/7 主要作用于病毒复制周期的吸附以及进入/融合阶段,MP Ⅲ-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-MP Ⅲ及其突变体MP Ⅲ-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-MP Ⅲ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.
Abstract
Objective To study the inhibitory activity of the wasp venom peptide Protopolybia-MP Ⅲand its optimized mu-tants MP Ⅲ-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-MP Ⅲ and 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 MP Ⅲ-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-MP Ⅲmainly acted on the attachment of HSV-1 replication;MP Ⅲ-3/14 mainly on the entry/fusion and post entry of the virus replication cycle;MP Ⅲ-4/7 mainly acted on the attachment and entry/fusion stages;MP Ⅲ-10 mainly on the attachment and entry stages.Conclusion This paper determined the inhibitory activity of Protopolybia-MP Ⅲand its mutants MP Ⅲ-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-MP Ⅲ.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Key words
Wasp venom peptide/Optimized mutants/Herpes simplex virus-1/Replication cycle引用本文复制引用
基金项目
国家自然科学基金青年基金(82204407)
湖北省科技厅自然科学研究项目(2023AFB296)
湖北医药学院青年学者培养项目(2021QDJZR019)
出版年
2024