笼型蛋白仿生纳米结构构建及抗病毒研究  

Construction of cage protein biomimetic nanostructures and the antiviral research

作　　者：袁嫕 王超[1] 郭琼 王刚[1] 谢志萍[1] 段招军[1] 郑丽舒[1] YUAN Yi;WANG Chao;GUO Qiong;WANG Gang;XIE Zhi-ping;DUAN Zhao-jun;ZHENG Li-shu(NHC Key Laboratory of Medical Virology and Viral Diseases,National Institute for Viral Disease Control and Prevention,Chinese Center for Disease Control and Prevention,Beijing 100052,China)

机构地区：[1]中国疾病预防控制中心病毒病预防控制所,国家卫生健康委员会医学病毒与病毒病重点实验室,北京100052

出　　处：《电子显微学报》2023年第1期6-12,共7页Journal of Chinese Electron Microscopy Society

基　　金：中国博士后科学基金面上项目(No.2018M641442)。

摘　　要：本研究利用笼型铁蛋白亚基的解聚和自组装过程,在蛋白酶促活性位点上仿生合成1~3 nm尺径可控的金纳米团簇,构建了新型高生物活性抗病毒纳米药物Au@HFn,使用多种电镜学方法对其形貌、结构进行了表征;在抗病毒功效方面,Au@HFn具有抑制HepG 2.2.15细胞HBV s/e抗原分泌和降低HBV核酸复制的效果,抑制效果随金团簇尺径增加而提高并与纳米药物的浓度呈正相关;在细胞毒性实验测试中,Au@HFn未发现有细胞毒性,且增高了细胞活力,具有很高的生物安全性。本研究提出了一种新的抗病毒纳米药物构建策略,相对传统小分子抗病毒药物,在提高药物生物兼容性、降低毒副作用和抗耐药性等方面具有较大的潜力和应用前景。Using the depolymerization and self-assembly process of caged ferritin subunits, we performed biomimetic synthesis of 1-3 nm size-controlled gold nanoclusters within protease-promoted sites, which constructs a new antiviral nano-drug Au@HFn with high biological activity. A variety of electron microscopy method were used to characterize its morphology and structure. In terms of antiviral efficacy, Au@HFn has the effect of inhibiting the secretion of HBV s/e antigen and HBV nucleic acid replication in HepG 2.2.15 cells. The inhibitory effect is positively correlated with the size of gold clusters. In the cytotoxicity experimental test, Au@HFn was found to have no cytotoxicity while increase cell viability, with high biological safety. This study proposes a new strategy for the construction of antiviral nano-drugs, which has great potentials and application prospects in improving drug biocompatibility, reducing toxic side effects and drug resistance compared with traditional small-molecule antiviral drugs.

关 键 词：笼型蛋白 自组装 仿生合成 纳米结构 抗病毒 

分 类 号：Q617[生物学—生物物理学] Q692