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用于 SARS-CoV-2 中和与检测的工程化超高亲和力合成抗体。

Engineered Ultra-High Affinity Synthetic Antibodies for SARS-CoV-2 Neutralization and Detection.

机构信息

Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL, United States.

Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL, United States; Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL, United States.

出版信息

J Mol Biol. 2021 May 14;433(10):166956. doi: 10.1016/j.jmb.2021.166956. Epub 2021 Mar 26.

Abstract

The Covid-19 pandemic is a centenarial global catastrophe. Similar events are likely to be recurring with more frequency in the future. The inability to control the virus' impact is caused by many factors, but the lack of a technology infrastructure to detect and impede the virus at an early stage are principal shortcomings. Using phage display mutagenesis, we have generated a cohort of high performance antibody fragments (Fabs) that can be used in a sensitive point of care (POC) assay and are potent inhibitors (IC-0.5 nM) to viral entry into cells. The POC assay is based on a split-enzyme (β-lactamase) complementation strategy that detects virus particles at low nM levels. We have shown that this assay is equally effective for detecting other viruses like Ebola and Zika. Importantly, its components can be freeze dried and stored, but becomes fully active when rehydrated.

摘要

新冠疫情是一场百年一遇的全球灾难。类似的事件在未来很可能会更频繁地发生。无法控制病毒的影响是由许多因素造成的,但缺乏早期发现和阻碍病毒的技术基础设施是主要的缺点。我们利用噬菌体展示技术,生成了一组高性能的抗体片段 (Fabs),可以用于敏感的即时检测 (POC) 分析,并且是有效的病毒进入细胞的抑制剂 (IC-0.5 nM)。该 POC 分析基于酶切互补 (β-内酰胺酶) 策略,可在低纳摩尔水平检测病毒颗粒。我们已经证明,该分析方法对于检测埃博拉和寨卡等其他病毒同样有效。重要的是,其组成部分可以冻干和储存,但在重新水合时会完全激活。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2022/7997149/89abf92a826c/ga1_lrg.jpg

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