SARS-CoVs 的受体结合域的生物物理演变
Vaibhav Upadhyay1, Sudipta Panja1, Alexandra Lucas1
1Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Biophysical journal
|October 28, 2023
概括
严重急性呼吸系统综合征 (SARS) -CoV-2受体结合域 (RBDs) 不那么稳定,并且比SARS-CoV RBDs更多. 稳定性,聚合性和结合性亲和性的这些差异对于开发有效的SARS-CoV-2疫苗至关重要.
科学领域:
- 病毒学 病毒学
- 生物物理学的生物物理.
- 疫苗开发 疫苗开发
背景情况:
- 冠状病毒 (CoV) 构成重大威胁,其中三种菌株 (SARS-CoV,MERS-CoV,SARS-CoV-2) 导致人类严重疾病.
- SARS-CoV和SARS-CoV-2利用它们的受体结合域 (RBD) 结合人类细胞上的ACE2受体.
- 了解RBD中的生物物理差异对于疫苗设计至关重要.
研究的目的:
- 为了研究SARS-CoV和SARS-CoV-2 RBDs之间的生物物理差异.
- 为了比较它们的结构,稳定性,聚合和功能.
- 为开发稳定的蛋白质亚单元疫苗提供信息.
主要方法:
- 对 SARS-CoV 和 SARS-CoV-2 RBD 的比较生物物理分析.
- 热力学稳定性的评估.
- 对聚合倾向的评估.
- 对ACE2受体的结合亲和力测量.
主要成果:
- 与SARS-CoV RBD相比,SARS-CoV-2 RBD在热力学上显著不太稳定.
- 与SARS-CoV RBD相比,SARS-CoV-2 RBD表现出更高的聚合倾向.
- 尽管稳定性较低,但SARS-CoV-2 RBD与ACE2结合,具有更高的亲和力和更高的结合同质性.
结论:
- 与SARS-CoV RBD相比,SARS-CoV-2 RBD具有不同的生物物理特性 (稳定性,聚合性,功能),源于受体结合基因的变化.
- 由于SARS-CoV-2 RBD的聚合增加和稳定性降低,因此需要进一步优化蛋白子单位疫苗的开发.
- 对于有效的SARS-CoV-2疫苗,建议采用结合稳定突变或先进配方查等策略.
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