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通过人工的人类单克隆抗体对抗SARS类病毒具有广泛和强大的活性

C Garrett Rappazzo¹, Longping V Tse², Chengzi I Kaku¹

¹Adimab, LLC, Lebanon, NH 03766, USA.

Science (New York, N.Y.)

|January 26, 2021

概括

研究人员设计了抗体来中和广泛的冠状病毒 (CoV). 一种变种ADG-2有效中和了SARS-CoV-2和相关病毒,在动物模型中提供了对严重呼吸系统疾病的保护.

科学领域:

病毒学和免疫学
药物发现和开发

背景情况:

新冠病毒 (CoV) 的反复传播需要采取广泛的对策.
严重急性呼吸道综合征冠状病毒2 (SARS-CoV-2) 构成严重的全球健康威胁.

研究的目的:

设计具有增强中和能力的SARS-CoV-2抗体.
评估针对沙贝科病毒的工程抗体的治疗潜力.

主要方法:

用定向进化来设计SARS-CoV-2抗体.
对一组沙贝科病毒的结合活性和中和效果进行了评估.
结构和生化研究阐明了抗体与表皮质相互作用的机制.
在SARS和COVID-19的免疫能力较强的小鼠模型中评估了有效性.

主要成果:

一个工程抗体,ADG-2,显示强烈的结合到不同的sarbecovirus受体结合域.
ADG-2 有效地中和了代表性的流行性沙贝科病毒.
结构分析显示ADG-2通过独特的结合角度识别了保存的表位.
在小鼠模型中,ADG- 2的预防性使用提供了完全的保护,预防了呼吸系统疾病和病毒载量.

结论:

ADG-2 是一种高强度,广泛中和的抗体候选对抗1类沙贝科病毒.
ADG-2在预防和治疗新出现的冠状病毒引起的感染方面具有显著的前景.

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