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一种基于结构和知识的组合方法,用于设计针对流感M2蛋白的通用scFv抗体

Ujjwal Kumar¹, Priya Goyal², Zaid K Madni¹

¹International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, 110067, India.

Journal of biomedical science

|July 25, 2023

概括

研究人员开发了新型单链可变片段 (scFv) 抗体,针对流感病毒的保存M2e. 这些抗体与M2e二分体结合并抑制病毒复制,提供潜在的通用流感疗法.

科学领域:

病毒学病毒学
免疫学免疫学免疫学
结构生物学结构生物学

背景情况:

流感病毒的进入依赖于血凝素与酸结合.
病毒复制是由M2质子通道促进的.
M2 ectodomain (M2e) 是通用流感抗体治疗的保存标.

研究的目的:

识别和表征新型单链可变片段 (scFv) 抗体,以对抗流感M2ectodomain (M2e).
阐明scFv与M2e结合的结构基础.
评估M2e特异性scFvs对流感病毒感染的治疗潜力.

主要方法:

对M2e的菌体显示抗体库的查.
结合性测试 (ELISA,BLI,流细胞计) 来确认scFv-M2e相互作用.
通过X射线晶体学来确定scFv-M2e复杂结构.
使用实时PCR和共聚焦显微镜评估抗病毒活性的传染性测试.

主要成果:

四个独特的scFv克隆证明与M2e和全长M2蛋白结合.
晶体结构显示M2e二聚体与scFv CDRs相互作用.
scFv AU1显著抑制了H1N1病毒后代从感染细胞中释放.

结论:

结构和生物化学研究证实scFv与M2e二元体结合.
提供了对M2e抗体识别的结构性见解.
证明了M2e向scFvs在限制病毒颗粒释放方面的潜力.

关键词:

共同结晶的情况流感病毒是流感病毒.M2离子通道蛋白和M2e离子通道二元化.简单的人类抗体 scFv 图书馆病毒回归病毒回归

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