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开发一种双特异的纳米体结合物广泛中和了多种SARS-CoV-2变体及其广泛中和的结构基础
Jing Yang1, Sheng Lin1, Zimin Chen1
1Department of Emergency Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
PLoS pathogens
|November 30, 2023
概括
新的纳米体 (Nb-015和Nb-021) 中和了SARS-CoV-2变种. 一种联合四价格格的形式,Nb-X2-Fc,显示了对包括Omicron在内的多种菌株的增强效能和宽度.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 生物技术是生物技术.
背景情况:
- 新出现的严重急性呼吸系统综合征冠状病毒2 (SARS-CoV-2) 变种,由于其增加的传染性和免疫规避,造成了重大公共卫生挑战.
- 广泛的治疗方法的开发对于对抗SARS-CoV-2不断变化的威胁至关重要.
- 由于其独特的结合性和生化特性,纳米体提供了有前途的治疗潜力.
研究的目的:
- 确定和描述针对SARS-CoV-2尖端受体结合域 (S-RBD) 的新型纳米体.
- 评估单个纳米体和新型四价联物对抗SARS-CoV-2变体的中和能力.
- 阐明纳米体介导病毒中和的结构基础.
主要方法:
- 针对SARS-CoV-2 S-RBD.的高亲和力纳米体 (Nb-015,Nb-021) 的分离和特征.
- 确定纳米体/S-RBD复合物的高分辨率晶体结构.
- 基于Fc的四价纳米体格式 (Nb-X2-Fc) 的构建和评估.
- 对各种SARS-CoV-2变种的中和范围和效力的评估.
主要成果:
- 确定了两个高亲和度纳米体,Nb-015和Nb-021,针对SARS-CoV-2 S-RBD上的不同的表位.
- 这两种纳米体都证明了对各种SARS-CoV-2菌株的有效中和.
- 结构分析揭示了纳米体与S-RBD的精确结合相互作用.
- 四价Nb-X2-Fc合物显著增强了中和功效和范围,包括对Omicron子系的活性.
结论:
- Nb-015和Nb-021是针对SARS-CoV-2的强有力的中和剂.
- 四价Nb-X2-Fc联合体是一个有前途的治疗候选人,具有广泛的活性.
- 对于SARS-CoV-2感染的治疗,NB-X2-Fc需要进一步调查和体内评估.
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