一种非天然广谱抗病毒多肽的发现、活性评价及作用机制研究  

Discovery, bioactivity evaluation and mechanism study of a non-natural broad-spectrum antiviral peptide

作　　者：梁国栋 李瑞娟 田阳丽 夏帅 马宇衡 LIANG Guodong;LI Ruijuan;TIAN Yangli;XIA Shuai;MA Yuheng(Key Laboratory for Candidate Drug Design and Screening Based on Chemical Biology,School of Pharmacy,Inner Mongolia Medical University,Hohhot 010110,China;Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100850,China;Key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS),School of Basic Medical Sciences,Fudan University,Shanghai 200032,China)

机构地区：[1]内蒙古医科大学药学院基于化学生物学的候选药物设计与筛选重点实验室,内蒙古呼和浩特010110 [2]军事科学院军事医学研究院,北京100850 [3]复旦大学基础医学院教育部/卫健委/医科院医学分子病毒学重点实验室,上海200032

出　　处：《沈阳药科大学学报》2023年第12期1598-1607,共10页Journal of Shenyang Pharmaceutical University

基　　金：内蒙古自治区自然科学基金资助项目(2023LHMS08045);内蒙古医科大学青年资助项目(YKD2023QN053)。

摘　　要：目的本文以MERS-CoV、H1N1和HIV-13种病毒Ⅰ型包膜蛋白中跨膜亚基的NHR区域为靶标,设计能够与靶标特异性结合并对3种病毒均发挥抑制活性的完全非天然广谱抗病毒多肽。方法对非天然多肽IIS序列优化改造并经Fmoc固相合成法获得目标肽,开展3种病毒的抑制活性测试,通过圆二色谱、分析型超离心和等温滴定量热实验研究目标肽与靶标的作用机制。结果目标肽对MERS-CoV、H1N1和HIV-13种病毒均具有抑制活性,能够与3种病毒的NHR区域作用阻止病毒的膜融合过程。结论本文建立以病毒膜融合过程为基础的非天然抗病毒多肽设计方法和评价思路,为广谱抗病毒药物的开发提供一种新兴且有效的研究路径。Objective To design an artificial antiviral peptide, which could exert inhibitory activities against all three viruses using the transmembrane subunit NHR region in the Class I enveloped proteins of MERS-CoV, H1N1 and HIV-1 as the targets.Methods The Peptide was obtained by Fmoc solid-phase synthesis method for the modification of artificial IIS sequence, and the inhibition activity of three viruses was tested.The mechanism of the peptide with target was investigated by circular dichroism, analytical ultracentrifugation and isothermal titration calorimetry experiments.Results The peptide exhibited broad-spectrum inhibitory activity against MERS-CoV,H1N1 and HIV-1 and was able to interact with the NHR region to prevent the viral membrane fusion process.Conclusion We establish a design method of artificial antiviral peptide based on viral membrane fusion process, and provide an emerging and effective research perspective for the development of broad-spectrum antiviral drugs.

关 键 词：非天然抗病毒多肽 病毒膜融合 六股螺旋 广谱性 

分 类 号：R914[医药卫生—药物化学]