一种超强的合成纳米体通过稳定不活跃的Spike来中和SARS-CoV-2
Michael Schoof1,2, Bryan Faust3,2,4,5, Reuben A Saunders3,6
1Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, CA, USA. michael@walterlab.ucsf.edu peter@walterlab.ucsf.edu aashish.manglik@ucsf.edu.
Science (New York, N.Y.)
|November 6, 2020
概括
科学家们开发了一种强大的纳米体,mNb6-tri,通过锁定Spike蛋白在不活跃状态中来中和SARS-CoV-2. 这种纳米体可以通过气溶直接进入肺部.
科学领域:
- 病毒学
- 免疫学
- 生物技术
背景情况:
- 严重急性呼吸道综合征冠状病毒2 (SARS-CoV-2) 使用其尖端蛋白质将ACE2受体与宿主细胞结合进入.
- 开发有效的这种相互作用的抑制剂对于对抗病毒感染至关重要.
研究的目的:
- 设计能够破坏SARS-CoV-2 Spike-ACE2相互作用的纳米体.
- 为潜在的治疗应用开发一种强效和稳定的SARS-CoV-2中和剂.
主要方法:
- 对酵母表面显示的合成纳米体序列库进行选.
- 电子显微镜 (cryo-EM) 用于对纳米体-Spike相互作用的结构分析.
- 多价纳米体的亲和成熟和结构导向设计.
主要成果:
- 识别了与SARS-CoV-2尖端蛋白结合的纳米体,从而诱导了不活跃的形状.
- 一个三价纳米体的开发,mNb6-tri,与斯派克的女性亲和力.
- 通过mNb6-tri证明SARS-CoV-2感染的皮科莫尔中和.
- 在气溶液化,冷化和热处理后证实mNb6-tri的稳定性和功能性.
结论:
- 通过准Spike蛋白质,工程化纳米体可以有效地中和SARS-CoV-2.
- 三价纳米体mNb6-tri是一种高度强大的中和剂,有可能通过气溶传递到呼吸道.
- mNb6- tri的稳定性表明它适用于各种治疗策略.
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