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一个由抗体准的SARS-CoV-2尖端蛋白增强感染性的部位
Yafei Liu1, Wai Tuck Soh2, Jun-Ichi Kishikawa3
1Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan; Laboratory of Immunochemistry, World Premier International Immunology Frontier Research Centre, Osaka University, Osaka 565-0871, Japan.
Cell
|June 17, 2021
概括
一些针对SARS-CoV-2尖端蛋白的N终端域 (NTD) 的抗体可以通过促进ACE2结合来意外增强病毒感染力. 这项研究确定了在严重的COVID-19患者中发现的NTD上的"增强感染性部位".
科学领域:
- 病毒学
- 免疫学
- 结构生物学
背景情况:
- 已知针对SARS-CoV-2尖端蛋白受体结合域 (RBD) 的抗体可以中和病毒.
- 抗体对其他尖端蛋白域,特别是N终端域 (NTD) 的功能影响仍然在很大程度上未被探索.
研究的目的:
- 研究抗单克隆抗体在RBD之外的影响.
- 识别可能影响病毒感染性或ACE2结合的SARS-CoV-2尖端蛋白的特定抗体点.
主要方法:
- 从2019年冠状病毒病 (COVID-19) 患者中查单克隆抗体.
- 突变分析以确定抗体识别点.
- 结构分析以确定抗体结合模式.
- 患者和供体样本中的抗体量化.
主要成果:
- 针对NTD的某些抗体诱导了开放的RBD构成,增强了对ACE2的蛋白结合,并增加了SARS-CoV-2的感染性.
- 鉴定出NTD的一个特定部位是这些增强感染性的抗体的目标.
- 这些增强抗体在严重的COVID-19患者中普遍存在,并且在未感染的个体中也检测到较低的水平.
结论:
- SARS-CoV-2 感染不仅会产生中和抗体,还会产生可以增强病毒感染性的抗体.
- 在NTD上确定增强感染性的部位代表了理解病毒病变和免疫反应的新目标.
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