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在SARS-CoV-2突起E406W突变体中发生的结构性变化逃脱了临床单克隆抗体尾酒

Amin Addetia¹, Young-Jun Park², Tyler Starr³

¹Molecular and Cellular Biology Graduate Program, University of Washington, Seattle, WA, USA; Department of Biochemistry, University of Washington, Seattle, WA, USA.

|June 10, 2023

概括

SARS-CoV-2 病毒正在进化,其受体结合域中的 E406W 突变改变了抗体识别. 这种演变影响了当前的COVID-19治疗和疫苗的有效性.

科学领域:

病毒学病毒学
结构生物学结构生物学
免疫学免疫学免疫学

背景情况:

严重急性呼吸道综合征冠状病毒2 (SARS-CoV-2) 继续演变,导致疫苗和先前感染的现有抗体反应的疗效降低.
特定的突变,如受体结合域 (RBD) 中的E406W,可以显著影响病毒中和.

研究的目的:

为了研究SARS-CoV-2 RBD E406W突变的结构和功能后果.
了解这种突变如何影响治疗单克隆抗体 (mAbs) 和疫苗引起的中和抗体对病毒表位的识别.

主要方法:

具有E406W突变的SARS-CoV-2 RBD的结构分析.
对治疗 mAbs 对突变病毒的中和能力的评估.
对疫苗引起的中和抗体影响的评估.

主要成果:

已经证明,E406W突变可以以性方式重塑RBD,改变关键表位.
这种突变取消了特定治疗单克隆抗体 (REGEN-COV和AZD1061) 的中和活性.
突变影响了疫苗引起的中和抗体的识别,而RBD仍然具有功能.

结论:

SARS-CoV-2 RBD 呈现出显著的结构和功能可塑性,使其能够持续进化.
新出现的SARS-CoV-2变种正在改变的抗原位点中积累突变,可能逃避当前的免疫反应.
了解这些进化动态对于开发下一代疗法和疫苗至关重要.

关键词:

在 COVID-19 疫情中,CP: 免疫学免疫学 CP: 微生物学微生物学这就是SARS-CoV-2病毒.低温电磁波冷却器 (Cryo-EM) 是一个非常好的方法.一个单克隆抗体.受体结合领域是受体结合领域.尖尖的葡萄糖蛋白质是什么

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