针对携带L452R突变的SARS-CoV-2变种的一种中和抗体的基于结构的优化
Yamin Chen1,2, Jialu Zha3, Shiqi Xu2,4
1Suzhou Medical College, Soochow University, Suzhou 215123, China.
Viruses
|April 27, 2024
概括
一种新的中和抗体Ab08-K99E有效中和SARS-CoV-2变种,包括那些具有L452R突变的变种. 基于结构的优化增强了抗体对不断演变的病毒菌株的有效性.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 结构生物学 结构生物学
背景情况:
- 中和抗体 (nAbs) 对于对抗SARS-CoV-2至关重要.
- 在SARS-CoV-2变种中的L452R突变构成了抗体逃生挑战.
- 之前的nAb Ab08显示对L452R变体的疗效降低.
研究的目的:
- 为了开发一种优化的nAb,克服L452R介导的抗体逃逸.
- 为了增强Ab08对抗SARS-CoV-2变种的中和作用力和结合亲和力.
主要方法:
- Ab08衍生品的基于结构的设计.
- Ab08-K99E.的生成和表征.
- 对伪病毒 (Delta,Omicron BA.1,BA.4/5) 的中和功效的评估.
- 对受体结合域 (RBDs) 的结合特性和亲缘关系的评估.
主要成果:
- Ab08-K99E显著增强了对L452R突变的Delta变种的中和功效.
- Ab08-K99E对原型,Omicron BA.1和BA.4/5伪病毒进行了改善的中和.
- 与Ab08.08相比,Ab08-K99E与原型,Delta和Omicron BA.4/5变体的RBD表现出更好的结合亲和力.
结论:
- Ab08-K99E是一种强大的优化nAb,对各种SARS-CoV-2变体有效.
- 基于结构的抗体优化是针对不断演变的病毒病原体开发治疗方法的成功策略.
相关概念视频
01:10Antibody Structure
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...
02:50Conjugated Proteins
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...