美国伊利诺伊大学Erik Procko团队设计出了能够增强与SARS冠状病毒2突刺蛋白结合的工程化人源ACE2蛋白。这一研究成果于2020年8月4日在线发表在《科学》上。
Title: Engineering human ACE2 to optimize binding to the spike protein of SARS coronavirus 2
Author: Kui K. Chan, Danielle Dorosky, Preeti Sharma, Shawn A. Abbasi, John M. Dye, David M. Kranz, Andrew S. Herbert, Erik Procko
Issue&Volume: 2020/08/04
Abstract: Abstract The spike protein S of SARS coronavirus 2 (SARS-CoV-2) binds ACE2 on host cells to initiate entry, and soluble ACE2 is a therapeutic candidate that neutralizes infection by acting as a decoy. Using deep mutagenesis, mutations in ACE2 that increase S binding are found across the interaction surface, in the N90-glycosylation motif and at buried sites. The mutational landscape provides a blueprint for understanding the specificity of the interaction between ACE2 and S and for engineering high affinity decoy receptors. Combining mutations gives ACE2 variants with affinities that rival monoclonal antibodies. A stable dimeric variant shows potent SARS-CoV-2 and -1 neutralization in vitro. The engineered receptor is catalytically active and its close similarity with the native receptor may limit the potential for viral escape.
DOI: 10.1126/science.abc0870
Source: https://science.sciencemag.org/content/early/2020/08/03/science.abc0870