关键词: ACE2 Computational design RBD SARS-CoV-2 Spike protein

Mesh : Humans Angiotensin-Converting Enzyme 2 / metabolism chemistry COVID-19 / virology diagnosis Magnetite Nanoparticles / chemistry Protein Binding Protein Engineering SARS-CoV-2 / metabolism Spike Glycoprotein, Coronavirus / metabolism genetics chemistry

来  源:   DOI:10.1021/acsabm.4c00222

Abstract:
As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues its global spread, the exploration of novel therapeutic and diagnostic strategies is still needed. The virus enters host cells by binding the angiotensin-converting enzyme 2 (ACE2) receptor through the spike protein. Here, we develop an engineered, small, stable, and catalytically inactive version of ACE2, termed miniature ACE2 (mACE2), designed to bind the spike protein with high affinity. Employing a magnetic nanoparticle-based assay, we harnessed the strong binding affinity of mACE2 to develop a sensitive and specific platform for the detection or neutralization of SARS-CoV-2. Our findings highlight the potential of engineered mACE2 as a valuable tool in the fight against SARS-CoV-2. The success of developing such a small reagent based on a piecewise molecular design serves as a proof-of-concept approach for the rapid deployment of such agents to diagnose and fight other viral diseases.
摘要:
随着严重急性呼吸系统综合症冠状病毒2(SARS-CoV-2)继续在全球传播,仍需要探索新的治疗和诊断策略.病毒通过刺突蛋白结合血管紧张素转换酶2(ACE2)受体进入宿主细胞。这里,我们开发了一个工程,小,稳定,和无催化活性的ACE2,称为微型ACE2(mACE2),旨在以高亲和力结合刺突蛋白。采用基于磁性纳米粒子的检测方法,我们利用mACE2的强结合亲和力来开发用于检测或中和SARS-CoV-2的敏感和特异性平台。我们的发现强调了工程化mACE2作为对抗SARS-CoV-2的有价值工具的潜力。基于分段分子设计开发这种小试剂的成功作为快速部署这种试剂以诊断和对抗其他病毒性疾病的概念验证方法。
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