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开发ACE2-热带-贝塔冠状病毒治疗药物,以应对未来的流行病

Ashley Utz^1,2,3, Matt Armbrust⁴, Thuy-Tien T Nguyen^2,5

¹Stanford Biophysics Program, Stanford University School of Medicine, Stanford, CA, USA.

Nature communications

|November 29, 2025

概括

新的ReconnAb-多元器件提供了对各种β冠状病毒的广泛中和,包括SARS-CoV-2变种. 这种治疗设计显示出克服病毒进化挑战和保护未来流行病的潜力.

科学领域:

病毒学病毒学
免疫学免疫学免疫学
治疗设计治疗设计

背景情况:

病毒遗传进化在流行病期间为开发有效的治疗方法提出了重大挑战.
随着SARS-CoV-2变种的出现,几种单克隆抗体 (mAb) 疗法变得无效,导致FDA取消紧急使用授权.

研究的目的:

引入ReconnAb-multimers,这是一种新的治疗策略,旨在广泛有效地中和betacoronaviruses.
评估ReconnAb-multimers对SARS-CoV-2变种和其他潜在的流行性β冠状病毒的疗效.

主要方法:

开发ReconnAb-复合剂,其中包含一种泛-贝塔冠状病毒抗体,向一种保存的尖端蛋白表位和一种催化无活性的ACE2组件.
对SARS-CoV-2伪病毒和真正的病毒变异引起关注 (VOC) 的中和效力的评估.
测试对相关的贝塔冠状病毒 (SARS-CoV,WIV1-CoV,PRD-0038,HKU5-CoV-2) 的中和和对小鼠的体内保护研究.

主要成果:

ReconnAb-multimers证明了对所有测试的SARS-CoV-2伪病毒和真实的VOC的强烈中和,与FDA批准的mAbs.相比或优于它们.
观察到针对SARS-CoV,WIV1-CoV,PRD-0038和HKU5-CoV-2的广泛中和.
在小鼠中,ReconnAb-multimers提供了对真实Omicron变异XBB.1.5挑战的保护,尽管其半衰期很短.

结论:

ReconnAb-复合剂代表了对当前和未来的ACE2-依赖性β冠状病毒的有希望的广谱治疗候选者.
这种设计有可能克服病毒逃生机制并减轻流行病威胁.

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