美洲大蠊抗病毒多肽研究

The American cockroach (Periplaneta Americana), also well known as “Xiao Qiang”, has incredible environmental adaptability and extremely strong vitality. Although it carries a variety of pathogenic bacteria, fungi, viruses, protozoa, and parasitic eggs, its powerful innate immune system makes cockroach significantly resistant to pathogenic microorganisms, including the Periplaneta fuliginosa densonucleosis virus. In addition, the cockroach is a kind of famous traditional Chinese medicine. It has been proved that the extracts of cockroach possess antiviral, antibacterial, anti-inflammatory, anti-tumor, tissue-repair, antioxidant, and immunity-improvement functions. The extracts of cockroach have been applied in the clinical treatment of Hepatitis B for its favorable antiviral ability to Hepatitis B Virus. The antiviral processes in both insect and human are related to the antiviral peptides. However, their mechanism and internal link remain unclear. Therefore, this project will screen novel antiviral peptides using bioinformatics and peptidomics techniques, investigate the antivirus function and mechanism of the antiviral peptide in cockroach immune system, and validate the therapeutic effect and mechanism of the antiviral peptide in the treatment hepatitis B. The results of this study will reveal the secret why cockroach is called “Xiao Qiang” by illuminating the underlying mechanism of its powerful immune system. The findings will also enlighten the mechanism of its clinical application to treat Hepatitis B, improve the therapeutic effects, and promote the development of traditional Chinese medicine.

美洲大蠊，俗称蟑螂，因其对环境惊人的适应性与顽强的生命力，素有“小强”之称。美洲大蠊具有强大的天生免疫能力，对黑胸大蠊病毒等致病微生物有显著的抵抗力，不容易被侵染。同时，美洲大蠊是我国的传统中药，其提取物具抗病毒等多种药用价值，在临床上用于乙肝治疗。美洲大蠊虫体自身抗病毒免疫能力和体外抗乙肝病毒活性均与抗病毒多肽阻止病毒侵染密切相关，但两者的作用机制及内在联系尚不清楚。本项目拟通过生物信息学与多肽组学筛选病毒诱导下的美洲大蠊抗病毒多肽；探讨抗病毒多肽在虫体中抵抗病毒致病的天生免疫机制；研究抗病毒多肽在细胞与小鼠模型中对抗乙肝病毒的药效和机理；最后确定美洲大蠊抗病毒多肽抵抗黑胸大蠊病毒和乙肝病毒的天生免疫内在联系。研究成果将进一步揭示美洲大蠊之所以称为“小强”的强大天生免疫系统的生命奥秘，阐释其在临床应用上抗乙肝病毒的作用机理，为弘扬和推动我国传统昆虫中医药的开发和利用奠定坚实的基础。

美洲大蠊具有强大的先天免疫系统，即使携带各种病原体，自身的生长发育却几乎不受影响，同时因其强大的抗逆性，常被用作一种传统的动物类中药。近年来的研究发现美洲大蠊提取物具有抗病毒、抗肿瘤、抗炎症、组织修复、抗氧化及增强免疫作用等巨大药用价值。宿主防御肽(Host Defensin Peptides, HDPs)是一类具有非特异性免疫功能的多肽，具有广谱的抗细菌、抗真菌、抗病毒、抗氧化、抗肿瘤和调节免疫等活性。本研究通过生物信息学手段对美洲大蠊HDPs进行结构与性能的预测分析，并选取具有潜在药用价值的美洲大蠊HDPs进行固相合成，随后检测其抗病毒活性。同时通过不同方法对美洲大蠊多肽进行提取，并检测其抗病毒活性。本研究从美洲大蠊基因组信息出发，通过生物信息学筛选获得7种具有抗病毒潜力的宿主防御肽，并对其结构、理化性质和抗微生物活性进行预测。随后选取其中的3种理论具有较好潜力的宿主防御肽进行固相合成。细胞和动物实验均证实其中一个美洲大蠊宿主防御肽PaDefensin5具有较佳的抗病毒效果。此外，对美洲大蠊进行初步提取，提取物也具抗病毒能力，且醇提物效果更强。本研究证明PaDefensins和美洲大蠊提取物均具有抗病毒活性，提示美洲大蠊具有较佳的药用价值，为将其开发和生产作为抗病毒药物提供理论依据。