在最近的SARS-CoV-2变种中抗原漂移的结构和功能影响
Meng Yuan1, Deli Huang2, Chang-Chun D Lee1
1Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Science (New York, N.Y.)
|May 21, 2021
概括
针对SARS-CoV-2尖端蛋白受体结合部位的中和抗体对新变种的有效性较低. 像E484K和K417N这样的突变显著降低了抗体的有效性,影响了疫苗和治疗的开发.
科学领域:
- 病毒学
- 免疫学
- 结构生物学
背景情况:
- 严重急性呼吸综合征冠状病毒2 (SARS-CoV-2) 变种在尖端蛋白的受体结合部位 (RBS) 呈现突变.
- 这些突变,特别是残留物Glu484,Lys417和Asn501,在B.1.351和P.1等变体中发现.
- 针对野生型RBS的中和抗体 (nAbs) 对于理解病毒免疫逃避至关重要.
研究的目的:
- 分析特定的SARS-CoV-2尖端蛋白突变 (E484K,K417N) 对血管激素转化酶2结合的影响.
- 评估这些突变对COVID-19患者抗体中和活性的影响.
- 了解SARS-CoV-2变体中抗体耐药性的结构基础.
主要方法:
- 分析SARS-CoV-2尖端蛋白的受体结合部位 (RBS) 的突变.
- 对血管素转化酶2的结合亲和度的评估.
- 使用COVID-19患者的抗体进行中和抗体结合和中和测定.
- 抗体与RBS相互作用的结构分析.
主要成果:
- 突变K417N和E484K显著降低了针对RBS的常见抗体家族 (IGHV3-53/3-66和IGHV1-2) 的结合和中和活性.
- 结构解释显示这些突变与向RBS的nAbs之间有广泛的相互作用,导致废除.
- 针对保存的交叉中和位点 (CR3022,S309) 的抗体在很大程度上不受这些突变的影响.
结论:
- 在SARS-CoV-2尖端蛋白中的特定突变可以逃避常见抗体家族的中和.
- 了解这些耐药机制对于设计有效的下一代疫苗至关重要.
- 抗体疗法可能需要重新评估或重新设计以克服变种特异性免疫逃避.
相关概念视频
01:28Diversity of Antigen Receptors
1.1K
Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
1.1K
03:33Genetic Drift
41.7K
Natural selection—probably the most well-known evolutionary mechanism—increases the prevalence of traits that enhance survival and reproduction. However, evolution does not merely propagate favorable traits, nor does it always benefit populations.
41.7K
01:09Mutation, Gene Flow, and Genetic Drift
60.5K
In a population that is not at Hardy-Weinberg equilibrium, the frequency of alleles changes over time. Therefore, any deviations from the five conditions of Hardy-Weinberg equilibrium can alter the genetic variation of a given population. Conditions that change the genetic variability of a population include mutations, natural selection, non-random mating, gene flow, and genetic drift (small population size).
60.5K
00:42Cross-reactivity
31.9K
Overview
31.9K
00:36Viral Mutations
36.5K
A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
36.5K
00:56Viral Structure
69.1K
Viruses are extraordinarily diverse in shape and size, but they all have several structural features in common. All viruses have a core that contains a DNA- or RNA-based genome. The core is surrounded by a protective coat of proteins called the capsid. The capsid is composed of subunits called capsomeres. The capsid and genome-containing core are together known as the nucleocapsid.
69.1K