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工程化人源ACE2蛋白可高效结合新冠病毒突刺蛋白
作者:小柯机器人 发布时间:2020/8/5 23:23:59

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。

使用深层诱变,研究人员在相互作用表面、N90-糖基化基序和掩埋位点发现了ACE2中增加突刺蛋白S结合的突变。突变情况为了解ACE2和S之间相互作用的特异性以及工程化高亲和力诱饵受体提供了一个蓝图。组合突变使ACE2变体具有可与单克隆抗体相媲美的亲和力。稳定的二聚体变体在体外显示出有效的SARS-CoV-2和-1中和作用。
 
该工程化受体具有催化活性,其与天然受体的紧密相似性可能会限制病毒逃逸的可能性。
 
据悉,SARS冠状病毒2(SARS-CoV-2)的突刺蛋白S与宿主细胞上的ACE2结合来启动进入,而可溶性ACE2是通过充当诱饵来中和感染的治疗候选物。
 
附:英文原文

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

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037