通过单域驼类抗体对贝塔冠状病毒进行有力的中和的结构基础
Daniel Wrapp1, Dorien De Vlieger2, Kizzmekia S Corbett3
1Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
Cell
|May 7, 2020
概括
研究人员开发了来自驼的单域抗体 (VHHs),可以中和MERS-CoV和SARS-CoV-1尖端蛋白. 交叉反应性VHH还可以中和SARS-CoV-2,为冠状病毒爆发提供潜在的治疗方法.
科学领域:
- 病毒学
- 免疫学
- 结构生物学
背景情况:
- 冠状病毒利用尖端 (S) 蛋白进入宿主细胞和膜融合.
- S蛋白质是开发抗病毒疗法的关键目标.
- 由于其稳定性和大小,单域抗体 (VHHs) 具有治疗作用的潜力.
研究的目的:
- 将针对冠状病毒S蛋白的VHHs分离和表征.
- 研究这些VHH对病原性β冠状病毒的中和能力.
- 探索VHH介导病毒中和的结构基础.
主要方法:
- 通过注射前稳定的冠状病毒尖峰对驼进行免疫接种.
- 单域抗体 (VHH) 的分离和表征.
- 使用MERS-CoV,SARS-CoV-1和SARS-CoV-2 S伪型病毒进行中和测定.
- 确定VHH-表位复合物的晶体结构.
主要成果:
- 已分离出可以中和MERS-CoV和SARS-CoV-1 S伪型病毒的VHH.
- 结构分析揭示了VHHs的独特表位,这两种表位都干扰受体结合.
- 一种SARS-CoV-1 S导向的VHH与SARS-CoV-2 S进行交叉反应,并且在格式化为双价IgG Fc融合时中和SARS-CoV-2 S伪型病毒.
结论:
- 通过向S蛋白,VHHs可以有效地中和致病性β冠状病毒.
- 已识别的VHH提供了对冠状病毒中和的分子理解.
- 这些VHH代表了对当前和未来的冠状病毒爆发进行治疗的有希望的候选人.
相关概念视频
00:42Cross-reactivity
32.7K
Overview
32.7K
01:10Antibody Structure
65.0K
Overview
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
65.0K