笼型蛋白仿生纳米结构构建及抗病毒研究

袁 嫕,王 超,郭 琼,王 刚,谢志萍,段招军*,郑丽舒*

笼型蛋白仿生纳米结构构建及抗病毒研究

袁  嫕,王  超,郭  琼,王  刚,谢志萍,段招军*,郑丽舒*

(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)

    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;在的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。

关键词 笼型蛋白;自组装;仿生合成;纳米结构;抗病毒

中图分类号:Q617;Q692;R511;R917  文章编号:A      doi:10.3969/j.issn.1000-6281.2023.01.002

 

Construction of cage protein biomimetic nanostructures and the antiviral research

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)

Abstract  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 methods 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.

Keywords   cage protein;self-assembly;biomimetic synthesis;nanostructures;antiviral

 

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