工程制造的热稳定三螺旋血管酶转化酶2多的广泛中和能力,准SARS-CoV-2的受体结合域
Davide Cavazzini1, Elisabetta Levati1, Saveria Germani2
1Laboratory of Biochemistry and Molecular Biology, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, 43124 Parma, Italy.
International journal of molecular sciences
|November 27, 2024
概括
工程 ACE2 片段,如 PRP8_3H,在中和 SARS-CoV-2 变种方面显示出有前途. 这种诱蛋白与病毒尖端蛋白结合,为新的COVID-19疫苗和疗法提供了潜力.
科学领域:
- 病毒学 病毒学
- 生物化学 生物化学
- 药物发现 药物发现 药物发现
背景情况:
- 包括Omicron在内的SARS-CoV-2变种由于尖端蛋白的突变而逃避当前的疫苗和治疗方法.
- 尖端蛋白上的ACE2受体结合部位是抗病毒策略的保留目标.
- 工程 ACE2 蛋白质和碎片可以作为诱来阻止病毒进入.
研究的目的:
- 为了生化表征和评估合理设计的ACE2 N-终端三螺旋碎片的抗病毒特性.
- 开发一种基于ACE2的稳定和强大的诱来中和SARS-CoV-2,包括当前的变种.
主要方法:
- 设计和重组生产具有稳定突变的ACE2 N端三螺旋碎片.
- 生物化学测试以评估热稳定性和与SARS-CoV-2尖峰受体结合域的结合亲和力.
- 在体外中和试验中使用表达武汉和Omicron尖端蛋白的伪病毒进行测试.
主要成果:
- 一个经过修改的片段,PRP8_3H,显示出对SARS-CoV-2尖端蛋白的高热稳定性和纳米分子亲和力.
- 在 (微小) 度下,PRP8_3H有效中和了表达武汉和Omicron尖端蛋白的伪病毒.
- 未经修改的ACE2碎片在热方面不稳定,缺乏中和能力.
结论:
- 合理设计的ACE2片段,特别是PRP8_3H,是针对SARS-CoV-2的强大而稳定的诱.
- PRP8_3H显示出作为新预防和治疗应用的原型,对当前和未来的病毒变异具有显著的潜力.
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