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广泛有效的ACE2诱蛋白保护小鼠免受致命的SARS-CoV-2感染

Mengjia Lu^1,2, Weitong Yao³, Yujun Li⁴

¹State Key Laboratory of Chemical Oncogenomics, Guangdong Provincial Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, Guangdong, China.

Microbiology spectrum

|July 3, 2023

概括

两种新型可溶性ACE2诱蛋白,ACE2-Ig-95和ACE2-Ig-105/106,对SARS-CoV-2变种表现出强大的广谱中和作用. 这些蛋白质在致命的COVID-19小鼠模型中提供了显著的保护,证明了作为有效疗法的潜力.

科学领域:

病毒学和免疫学病毒学和免疫学
生物技术和药物开发

背景情况:

具有耐药性的SARS-CoV-2变种的出现需要开发广泛有效的抗病毒药物.
作为受体诱设计的可溶性ACE2蛋白质代表了阻止病毒进入和感染的有希望的策略.

研究的目的:

进一步开发和描述两个SARS-CoV-2受体诱蛋白,即ACE2-Ig-95和ACE2-Ig-105/106.
评估它们对各种SARS-CoV-2变体的中和效能及其在严格的临床前模型中的有效性.
为设计广泛有效的ACE2诱疗法提供有关关键因素的见解.

主要方法:

对各种SARS-CoV-2变种的ACE2-Ig-95和ACE2-Ig-105/106体外中和活动的表征.
在致命的SARS-CoV-2感染小鼠模型中评估治疗疗效,测量病毒载量,临床症状和生存率.
与之前描述的ACE2-Ig结构进行对比,并评估其可开发性和稳定性.

主要成果:

ACE2-Ig-95和ACE2-Ig-105/106表现出强大的体外中和作用,对抗SARS-CoV-2变种,包括BQ.1和XBB.1.
在小鼠模型中,这些蛋白质显著降低了肺病毒载量,在75%以上的动物中预防了临床症状,并将生存率提高到>87.5%.
在RBD结合接口附近广泛的ACE2突变降低了中和效能;蛋白质可以在克/升尺度上生产,但需要稳定性改进.

结论:

ACE2-Ig-95和ACE2-Ig-105/106是强大的候选药物,可以广泛保护SARS-CoV-2变种和严重的COVID-19.
该研究强调了仔细设计ACE2诱的重要性,避免在RBD结合接口附近发生广泛的突变.
这些发现为临床前开发广泛有效的ACE2诱疗法对抗使用ACE2的冠状病毒提供了宝贵的见解.

关键词:

这就是ACE2ACE2.这是ACE2-Ig.这就是Omicron.这就是SARS-CoV-2病毒.致命的感染致命的感染.鼠标模型鼠标模型鼠标模型吸引受体的诱惑吸引受体的诱惑变异的担忧变体

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