在抗SARS-CoV-2尖端蛋白单克隆抗体中具有ACE-2类酶活性
bioRxiv : the preprint server for biology
|February 12, 2026
概括
针对SARS-CoV-2尖端蛋白的某些抗体可能模仿ACE2,可能导致长期COVID (LC) 病原体. 这些类似ACE2的亚基酶与原生ACE2不同地切割血管新生素II,为COVID-19的后果提供了新的见解.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 生物化学 生物化学
背景情况:
- COVID-19 (PASC/长期COVID) 后急性后续症状带来了重大的公共卫生挑战,症状包括血压调节失调和神经精神病的投诉.
- 长期COVID病原体的确切机制尚不清楚.
- SARS-CoV-2病毒使用ACE2受体启动感染,通过其尖端蛋白受体结合域 (RBD) 结合.
研究的目的:
- 测试反RBD抗体可能具有类似ACE2的催化活性,从而导致长期COVID的假设.
- 研究这些类似ACE2的亚基酶在COVID-19及其后续病变发生过程中的潜在作用.
主要方法:
- 从多个来源对抗SARS-CoV-2尖端蛋白的人类单克隆抗体 (mAbs) 的查.
- 在确定的mAbs中描述ACE2类催化活性,包括动力学研究和抑制试验.
- 抗体活性与原生人类ACE2功能的比较.
主要成果:
- 在选的抗体中发现了四种具有ACE2类催化活性的人类mAbs.
- 与原生ACE2相比,这些mAbs通过不同的机制分裂血管新生素II,表现出不同的动力学参数 (Vmax,Km).
- 抗体活性没有受到MLN-4760或EDTA的抑制,与原生ACE2不同,但受到尖峰的抑制.
结论:
- 鉴定具有ACE2类催化活性的mAbs支持了SARS-CoV-2诱导的抗体可以调解COVID-19和长期COVID病原体的假设.
- 作为对传染病原体的反应产生的催化抗体可能在疾病发展中发挥更广泛的作用.
- 对这些类似ACE2的酶的进一步研究可以阐明长期COVID机制,并为治疗策略提供信息.
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