Engineering an ACE2-Derived Fragment as a Decoy for Novel SARS-CoV-2 Virus.
Engineering an ACE2-Derived Fragment as a Decoy for Novel SARS-CoV-2 Virus.
复制标题
DOI：
10.1021/acsptsci.2c00180
复制
发表时间：
2023-05
影响因子：
6
通讯作者：
F. Renzi;Austin Seamann;Koelina Ganguly;K. Pandey;S. Byrareddy;S. Batra;Sushil Kumar;D. Ghersi
中科院分区：
文献类型：
--
作者：
F. Renzi;Austin Seamann;Koelina Ganguly;K. Pandey;S. Byrareddy;S. Batra;Sushil Kumar;D. Ghersi
进入抑制剂是对新出现的病原体如新型SARS-CoV-2的反应中的重要资源，其通过表面刺突糖蛋白和细胞膜受体血管紧张素转换酶2（ACE 2）之间的相互作用进入人类细胞。使用的穗ACE 2，对接实验，和分子动力学模拟的结合表面的比较结构分析的组合，我们确定了一个稳定的片段ACE 2结合穗，是可溶性的，并没有预测到其生理配体血管紧张素II结合。从这个片段中，我们计算设计和实验验证了一个较小的，稳定的肽，破坏ACE 2刺钉相互作用在纳摩尔浓度，这表明其潜在的用途作为诱饵，可以干扰病毒的竞争结合。
Entry inhibitors are an important resource in the response against emerging pathogens like the novel SARS-CoV-2, which enters human cells via interaction between the surface spike glycoprotein and the cellular membrane receptor angiotensin-converting enzyme 2 (ACE2). Using a combination of comparative structural analyses of the binding surface of the spike to ACE2, docking experiments, and molecular dynamics simulations, we identified a stable fragment of ACE2 that binds to the spike, is soluble, and is not predicted to bind to its physiological ligand angiotensin II. From this fragment we computationally designed and experimentally validated a smaller, stable peptide that disrupts ACE2-spike interaction at nanomolar concentrations, suggesting its potential use as a decoy that could interfere with viral binding by competition.