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Yanqun Wang¹, Zhaoyong Zhang², Minnan Yang³

¹State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China; GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China; Clinical Laboratory Medicine Department, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

|January 4, 2024

概括

一个新的抗体,5817,中和了多个SARS-CoV-2变体,包括Omicron和相关的sarbecoviruses. 这种广泛的抗体向一个保存的表位,提供潜在的保护对未来的变异的关注.

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:

新兴的SARS-CoV-2变种,如Omicron,表现出对疫苗的耐受性,限制了现有的治疗抗体的有效性.
包括SARS-CoV-2在内的sarbecoviruses具有显著的序列相似性,这构成了未来跨物种传播和疫情的风险.

研究的目的:

识别和表征一种具有广泛中和能力的新型抗体,用于对抗SARS-CoV-2变种和相关的sarbecoviruses.
阐明抗体与表皮质相互作用的结构基础,用于广泛的中和抗体.

主要方法:

对抗SARS-CoV-2变种和sarbecoviruses的广泛中和抗体的查.
低温电子显微镜 (cryo-EM) 用于确定抗体-尖端蛋白质复合物的结构.
在体内研究以评估抗体在小鼠模型中的预防和治疗疗效.

主要成果:

抗体5817对SARS-CoV-2令人担忧的变体 (VOC),SARS-CoV和相关的蝙蝠/松鼠病毒进行了广泛的中和.
化EM显示,5817向受体结合域 (RBD) 开放状态中的高度保守的神秘表位,与其他抗体类别不同.
5817没有显示对Omicron及其子变体的功效损失,并在小鼠中提供了对多个SARS-CoV-2菌株和SARS-CoV的保护.

结论:

抗体5817是有前途的治疗候选者,因为它对各种类型的萨尔贝科病毒具有广泛的中和活性.
鉴定了一种保存的神秘表位,为开发下一代抗体来对抗先前出现的SARS-CoV-2变种提供了潜在的策略.
这一发现对于应对未来的冠状病毒威胁的准备至关重要.

关键词:

CP: 免疫学免疫学保存的表观原型.在活体中,活体中鼠标模型鼠标模型鼠标模型中和抗体的抗体中和.受体结合领域是受体结合领域.沙贝科病毒 (Sarbecovirus) 是一种病毒.

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