设计一种"粘液捕捉"的ACE2-免疫球蛋白混合体,具有皮科莫尔亲和力,作为COVID-19的吸入式泛变异免疫疗法
Karthik Tiruthani1, Carlos Cruz-Teran1, Jasper F W Chan2,3
1Division of Pharmacoengineering and Molecular Pharmaceutics University of North Carolina at Chapel Hill Chapel Hill North Carolina USA.
Bioengineering & translational medicine
|July 22, 2024
概括
一种新的ACE2-Fc合物,ACE2-(G4S) 6-Fc,作为一个强大的诱来中和SARS-CoV-2. 这种吸入免疫疗法有效地降低了子的病毒载量,显示了COVID-19治疗的前景.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 药物开发 药物开发
背景情况:
- 可溶性 ангиотензин转化酶2 (ACE2) 通过阻止病毒尖端蛋白从宿主细胞结合中中和SARS-CoV-2.
- 现有的ACE2-Fc诱在结合亲和力和中和力方面存在局限性.
研究的目的:
- 设计和评估一种新的"粘膜捕获"ACE2-Fc合物,ACE2-(G4S) 6-Fc,用于增强SARS-CoV-2中和.
- 评估ACE2-(G4S) 6-Fc作为针对SARS-CoV-2的吸入性免疫疗法的疗效.
主要方法:
- 结构性见解指导了ACE2-(G4S) 6-Fc的设计,通过灵活的链接器将截断的ACE2与粘素结合的IgG1-Fc连接起来.
- 对伪病毒和活体SARS-CoV-2进行了结合亲和力和中和力测试.
- 在实验室中评估了粘液捕获和雾化稳定性.
- 在体内有效性通过在SARS-CoV-2感染的仓鼠中通过鼻腔给药来评估.
主要成果:
- ACE2-(G4S) 6-Fc表现出皮科莫拉结合亲和力和对SARS-CoV-2的强效中和.
- 结合物有效地将病毒样颗粒困在人体呼吸道粘液中,并且在雾化时稳定.
- 哈姆斯特犬的鼻腔内注射剂量减少了感染后2天的鼻腔病毒载量10倍.
结论:
- 与传统诱相比,ACE2-(G4S) 6-Fc具有优越的结合和中和特性.
- 粘液陷设计和吸入输送显示了COVID-19的显著治疗潜力.
- 这种方法可能适用于其他利用ACE2进入细胞的病毒.
相关概念视频
02:50Conjugated Proteins
Simple proteins and protein complexes contain only amino acids. In contrast, many other proteins, called conjugated proteins, covalently bond with non-protein moieties.
Nucleoproteins are protein complexes that contain nucleic acids, categorized as deoxyribonucleoproteins (DNPs) or ribonucleoproteins (RNPs) respectively. The nucleosome is a typical example of a DNP where nuclear DNA is associated with histone proteins. The major antigen for the Covid-19 virus SARS-CoV is an RNP that is critical...
Nucleoproteins are protein complexes that contain nucleic acids, categorized as deoxyribonucleoproteins (DNPs) or ribonucleoproteins (RNPs) respectively. The nucleosome is a typical example of a DNP where nuclear DNA is associated with histone proteins. The major antigen for the Covid-19 virus SARS-CoV is an RNP that is critical...
01:29Coronavirus
Coronaviruses, including the severe acute respiratory syndrome coronavirus (SARS-CoV), are enveloped viruses characterized by their single-stranded, positive-sense RNA genome and helical nucleocapsid structure. The hallmark of these viruses is their club-shaped spike (S) glycoproteins that protrude from the viral envelope, facilitating attachment to host cells. Typically, coronaviruses infect the upper respiratory tract, often causing mild or asymptomatic disease. However, certain strains like...