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针对SARS-CoV-2尖端蛋白的三价纳米体集群的结构导向设计

Xinyi Jiang¹, Qin Qin¹, Haixia Zhu¹

¹State Key Laboratory of Genetic Engineering, Shanghai Engineering Research Center of Industrial Microorganisms, MOE Engineering Research Center of Gene Technology, School of Life Sciences, Fudan University, Shanghai 200438, China.

International journal of biological macromolecules

|November 24, 2023

概括

研究人员设计了一种三价纳米体集群,Tribody,用于增强与SARS-CoV-2尖端蛋白的结合. 这种结构导向的设计显著提高了抗病毒中和,提供了对冠状病毒有前途的新疗法策略.

科学领域:

生物化学和结构生物学.
免疫学和病毒学.
药物发现和蛋白质工程.

背景情况:

纳米体是针对SARS-CoV-2的有效药物候选物.
多价纳米体增强了结合亲和力,但往往缺乏合理设计.
针对病毒蛋白的多个部位是提高疗效的关键.

研究的目的:

为多价值纳米体开发结构导向的,合理的设计.
为了设计一个自我组装的三价纳米体集群,针对SARS-CoV-2尖端蛋白.
评估工程纳米体集群的结合亲和力和抗病毒活性.

主要方法:

使用分子动力学模拟的结构导向设计.
选择人类衍生的三元化支架和最佳链接器.
基于纳米体Nb6.6的三价纳米体集群 (Tribody) 的工程.
电子显微镜 (cryo-EM) 用于对三体尖复合物的结构性确定.

主要成果:

工程三体显示出超高的结合亲和力 (K_D <1 pM).
与单价纳米体Nb6.6相比,Tribody实现了对SARS-CoV-2伪病毒的中和率增加900倍.
冷-EM结构证实了Tribody与三个受体结合域 (RBD) 的同时结合,将它们锁定在一个3-RBD-向下构造中.

结论:

理性,结构引导的设计使得强大的合成纳米体集群的创建成为可能.
三体体代表了对抗SARS-CoV-2感染的有前途的蛋白质治疗候选者.
自组装的纳米体集群为开发下一代抗病毒药物提供了可行的策略.

关键词:

一个纳米人体.这就是SARS-CoV-2病毒.结构导向设计是指导结构的设计.合成抗体是一种合成抗体.

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Conjugated Proteins

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