针对SARS-CoV-2感染,从人类ACE2中获得的潜在中和的计算和实验识别
Qiaobin Yao1, Vidhyanand Mahase1, Wangheng Hou2
1Department of Biology, Howard University, Washington, DC, USA.
研究人员确定了人类ACE2中与SARS-CoV-2相互作用的关键区域,导致中和的发展. 这些体对武汉和Omicron两种变体都有潜在的治疗作用,为抗击COVID-19提供了一个有前途的战略.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 药物发现 药物发现 药物发现
背景情况:
- 人体 ангиотензин转化酶2 (hACE2) 是SARS-CoV-2进入的主要受体.
- ACE2多态性可以影响SARS-CoV-2的结合亲和力,影响感染易感性.
- 之前的研究已经确定了SARS-CoV-2尖端蛋白和ACE2中的关键残留物,用于病毒结合.
研究的目的:
- 探索HaCE2衍生中和作为对抗SARS-CoV-2的治疗策略.
- 调查ACE2多形态对与SARS-CoV-2尖刺蛋白的结合亲缘关系的影响.
- 评估针对包括Omicron在内的SARS-CoV-2变体的鉴定的潜在疗效.
主要方法:
- 计算和突变发生被用来选所有可能的ACE2误解突变,影响与SARS-CoV-2武汉-S1复合体结合.
- 通过计算确定了ACE2-RBD相互作用的六个重要的ACE2区域.
- 与这些区域相对应的被合成并使用伪型病毒颗粒和点滴测试测试结合和抑制作用.
主要成果:
- 在ACE2残留物D355和Y41的突变减弱了结合亲和力,而N330和D30则增强了它.
- 三种合成的表明与SARS-CoV-2 S蛋白结合,四种表现出抑制作用.
- 对武汉和Omicron S1复合物的比较分析表明了类似的结合模式,表明对Omicron变种的潜在有效性.
结论:
- 在 hACE2 内的六个区域对于与SARS-CoV-2 Spike 蛋白的受体结合域的相互作用至关重要.
- 由haCE2衍生而来的可以作为治疗药物,具有证明对SARS-CoV-2的结合和抑制活性.
- 已识别的可能对Omicron变体有效,对SARS-CoV-2具有广泛的治疗潜力.
更多相关视频
08:41Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-2
Published on: November 5, 2021
10:25Detection of SARS-CoV-2 Neutralizing Antibodies using High-Throughput Fluorescent Imaging of Pseudovirus Infection
Published on: June 5, 2021
相关概念视频
Peptide Identification Using Tandem Mass Spectrometry
This technique helps gather information regarding the protein from which the peptide was obtained and to study the peptides’ amino acid sequence. Identifying peptides from a complex mixture is an important component of the growing field of...
Peptide Bonds
Acids, Bases and Neutralization Reactions
Acids, Bases and Neutralization Reactions
Cell Potential and Free Energy
Thermodynamics is the branch of physics dealing with the relationship between heat and other forms of energy. In an electrochemical cell, chemical energy is converted into electrical energy.
Thus, a link can be predicted between cell potential, free energy change, and the equilibrium constant for the reaction. Cell potential can also be measured as the oxidant or the reducing strength, and similar acid-base strength measures are reflected in equilibrium...
Loss of Carboxy Group as CO2: Decarboxylation of Malonic Acid Derivatives
