SARS-CoV-2 变种对 LCB1及其多价值衍生物的敏感性和耐药性
Hongliang Jin1, Yani Gong1, Lin Cheng2
1NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 102600, China.
Viruses
|January 23, 2024
概括
多价值LCB1融合蛋白显示出增强的SARS-CoV-2抑制,但面临来自XBB等变体的抗性. 这些抑制剂对蝙蝠和松鼠冠状病毒有效,为广泛的抗病毒药物提供了潜力.
科学领域:
- 病毒学 病毒学
- 蛋白质工程是指蛋白质工程.
- 药物发现 药物发现 药物发现
背景情况:
- SARS-CoV-2 变种对现有的抗病毒疗法构成威胁.
- LCB1是一种小型蛋白质,旨在准SARS-CoV-2尖端蛋白的RBM.
- 耐药变异的出现需要开发改进的抑制剂.
研究的目的:
- 为增强SARS-CoV-2抑制设计和评估多价值LCB1融合蛋白 (LCB1T和LCB1T-Fc).
- 评估这些融合蛋白对各种SARS-CoV-2变种和其他冠状病毒的疗效.
- 调查变异对抑制剂通过ACE2阻止病毒进入的能力的影响.
主要方法:
- 构建和表征LCB1T和LCB1T-Fc融合蛋白.
- 在体外抑制试验中,使用SARS-CoV-2伪病毒和真实病毒进行测试.
- 对一组SARS-CoV-2变种进行测试,包括Delta,Omicron BQ.1.1,XBB,XBB.1.5和EG.5.1.1.
- 对蝙蝠冠状病毒RaTG13和松鼠冠状病毒PCoV-GD/PCoV-GX的抑制的评估.
- 评估LCB1融合蛋白对RBD/S-ACE2相互作用的阻断能力.
主要成果:
- 与LCB1相比,LCB1融合蛋白对SARS-CoV-2的抑制活性有所改善.
- 变种Omicron BQ.1.1,XBB,XBB.1.5和EG.5.1表现出不同程度的抗性,XBB系变种表现出高水平的抗性.
- 与LCB1不同的是,LCB1融合蛋白有效抑制蝙蝠和松鼠冠状病毒,与LCB1不同.
- 该XBB变体显著降低了融合蛋白阻断ACE2结合的能力.
结论:
- 多价值LCB1融合蛋白提供增强的抗病毒效能和更广泛的冠状病毒活性.
- 变异性耐药性,特别是来自XBB血统的耐药性,是这些抑制剂的重大挑战.
- 基于LCB1的抑制剂的进一步开发是新型广谱抗病毒疗法的有希望的策略.
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