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ACE2 结合使 SARS-CoV-2 融合暴露在广泛中和的冠状病毒抗体中
Jun Siong Low1,2, Josipa Jerak1,2, M Alejandra Tortorici3
1Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland.
概括
研究人员确定了7种强大的单克隆抗体 (mAbs),针对冠状病毒的保存融合. 这些抗体可以中和SARS-CoV-2变种,并减少体内病毒载量,提供新的治疗途径.
科学领域:
- 病毒学
- 免疫学
- 结构生物学
背景情况:
- 冠状病毒尖端糖蛋白对于宿主细胞进入和病毒融合至关重要.
- 在各种冠状病毒中识别保存目标是广泛的抗病毒策略的关键.
研究的目的:
- 单克隆抗体 (mAbs) 的分离和特征,针对冠状病毒尖端蛋白的保护区域.
- 评估这些mAbs对包括SARS-CoV-2变种在内的各种人类和动物冠状病毒的中和能力和治疗潜力.
主要方法:
- 从SARS-CoV-2免疫捐赠者的单克隆抗体进行广泛查.
- 针对α和β冠状病毒的体外中和测定.
- 在体内研究以评估病毒负荷和病理减轻.
- 抗体与表皮质相互作用的结构和功能分析.
主要成果:
- 隔离了7个识别融合的mAbs,证明它们与感染人类的冠状病毒尖端蛋白广泛结合.
- 选择的mAbs在体外对包括Omicron BA.1和BA.2在内的各种冠状病毒具有强烈的中和作用.
- 两种mAbs在体内有效降低病毒负荷和病理.
- 结构研究揭示了ACE2受体结合时暴露在尖端蛋白质上的神秘表位的独特结合方式.
结论:
- 针对保存的融合的单克隆抗体可以实现广泛的冠状病毒中和.
- 这些融合特异性mAbs代表了开发针对当前和未来的冠状病毒威胁的广泛抗病毒疗法的有希望的候选人.
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