ACE2,从脏到SARS-CoV-2:唐纳德·塞尔丁2023年颁奖演讲
Daniel Batlle1, Luise Hassler1, Jan Wysocki1
1Division of Nephrology/Hypertension, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Hypertension (Dallas, Tex. : 1979)
|December 3, 2024
概括
可溶性 ангиотензин转化酶2 (ACE2) 蛋白质通过向脏宁- ангиотензин系统和中和SARS-CoV-2提供双重治疗潜力. 生物工程可溶性ACE2提供了对SARS-CoV-2变种的保护.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 病毒学 病毒学
背景情况:
- ангиотензин转化酶2 (ACE2) 是一种关键的酶,可以代谢 ангиотензин II (Ang II),并作为 SARS-CoV-2 的细胞受体.
- 膜结合的ACE2具有脏保护作用,而可溶性ACE2可能具有治疗效益.
- ACE2的双重作用为心血管和传染病提供了一个独特的治疗点.
研究的目的:
- 开发可溶性ACE2截断剂,针对脏宁-血管素系统.
- 设计一种具有增强SARS-CoV-2结合亲和力和长时间作用的可溶性ACE2蛋白.
- 为了评估生物工程可溶性ACE2对SARS-CoV-2感染的治疗疗效.
主要方法:
- 针对脏的ACE2截断器的设计.
- 一种可溶性ACE2蛋白 (ACE2 618-DDC-ABD) 的生物工程,具有改进的SARS-CoV-2结合.
- 在感染SARS-CoV-2变种的k18hACE2小鼠中注射ACE2 618-DDC-ABD.
主要成果:
- 工程化可溶性ACE2 (ACE2 618-DDC-ABD) 显示了对SARS-CoV-2的结合亲和力增加.
- 在感染SARS-CoV-2的小鼠中,鼻内注射提供了几乎完全的抗致死性保护.
- 可溶性ACE2蛋白显示出立即作用和针对多种SARS-CoV-2变异的广泛疗效.
结论:
- 可溶性ACE2蛋白是SARS-CoV-2中和的有效治疗剂.
- 基于ACE2的疗法为当前和新兴的SARS-CoV-2变种提供了通用方法.
- 准ACE2对治疗脏疾病和病毒感染有很大的希望.
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