RBD-E77 Fab复合体的结构揭示了SARS-CoV-2的中和和免疫逃脱
Zhichao Zhang1, Xiaoxiong Li1, Ying Xue1
1College of Life Sciences, Shanxi Agricultural University, Taiyuan 030031, People's Republic of China.
Acta crystallographica. Section D, Structural biology
|July 10, 2023
概括
一种新的单克隆抗体,E77,有效地中和SARS-CoV-2,但由于硬质障碍,对N501Y突变的变体失去了有效性,影响了抗体的发展.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
背景情况:
- SARS-CoV-2 尖端蛋白的受体结合域 (RBD) 对于病毒进入至关重要,也是疫苗和抗体的关键目标.
- 对SARS-CoV-2关注变种 (VOCs) 的RBD突变对现有的抗体疗法和疫苗有效性构成重大挑战.
研究的目的:
- 为了表征一种新的小鼠单克隆抗体,E77,针对SARS-CoV-2 RBD.
- 调查E77中和活性的结构基础及其对VOCsRBD突变的敏感性.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来确定与SARS-CoV-2 RBD复合的E77抗体片段 (Fab) 的结构.
- 使用代表不同SARS-CoV-2变异的伪病毒进行了结合亲和和中和试验.
主要成果:
- 单克隆抗体E77与SARS-CoV-2 RBD原型结合,具有高度亲和力,并有效中和伪病毒.
- 通过N501Y突变消除了E77与RBD的结合,这种突变存在于Alpha,Beta,Gamma和Omicron等VOC中,但不是Delta.
- 结构分析显示,E77与RBD-1表位结合,与ACE2结合部位重叠,其CDRL1循环与Asn501相互作用,其中N501Y突变导致了硬质障碍.
结论:
- 在SARS-CoV-2 VOC中的N501Y突变会使E77与RBD结合,从而解释其失去了中和功效.
- 了解这些结构相互作用对于设计下一代抗体至关重要,这些抗体能够克服病毒免疫逃生机制.
关键词:
在 COVID-19 疫情中,在RBD中,RBD是RBD.这就是SARS-CoV-2病毒.挥发性有机化合物 挥发性有机化合物这种抗体是E7777抗体.可能是MABS.受体结合领域是受体结合领域.有关关注的变种.更多相关视频
08:07A "Plug-And-Display" Nanoparticle Vaccine Platform Based on Outer Membrane Vesicles Displaying SARS-CoV-2 Receptor-Binding Domain
Published on: July 25, 2022
2.6K
08:07Author Spotlight: Advancing Antiviral Strategies Through Novel Immunocapture and Mass Spectrometry Techniques
Published on: January 12, 2024
782
相关概念视频
02:50Conjugated Proteins
18.4K
Simple proteins and protein complexes contain only amino acids. In contrast, many other proteins, called conjugated proteins, covalently bond with non-protein moieties.
Nucleoproteins are protein complexes that contain nucleic acids, categorized as deoxyribonucleoproteins (DNPs) or ribonucleoproteins (RNPs) respectively. The nucleosome is a typical example of a DNP where nuclear DNA is associated with histone proteins. The major antigen for the Covid-19 virus SARS-CoV is an RNP that is critical...
Nucleoproteins are protein complexes that contain nucleic acids, categorized as deoxyribonucleoproteins (DNPs) or ribonucleoproteins (RNPs) respectively. The nucleosome is a typical example of a DNP where nuclear DNA is associated with histone proteins. The major antigen for the Covid-19 virus SARS-CoV is an RNP that is critical...
18.4K
01:29Viruses with RNA Genomes
57
RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
57