@article{db1649c67d67458da711d15d4a448b06,
title = "An engineered decoy receptor for SARS-CoV-2 broadly binds protein S sequence variants",
abstract = "The spike S of SARS-CoV-2 recognizes ACE2 on the host cell membrane to initiate entry. Soluble decoy receptors, in which the ACE2 ectodomain is engineered to block S with high affinity, potently neutralize infection and, because of close similarity with the natural receptor, hold out the promise of being broadly active against virus variants without opportunity for escape. Here, we directly test this hypothesis. We find that an engineered decoy receptor, sACE22.v2.4, tightly binds S of SARS-associated viruses from humans and bats, despite the ACE2-binding surface being a region of high diversity. Saturation mutagenesis of the receptor-binding domain followed by in vitro selection, with wild-type ACE2 and the engineered decoy competing for binding sites, failed to find S mutants that discriminate in favor of the wild-type receptor. We conclude that resistance to engineered decoys will be rare and that decoys may be active against future outbreaks of SARS-associated betacoronaviruses.",
keywords = "Coronavirus, COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Novel coronavirus, 2019-nCoV, Pandemic",
author = "Chan, {Kui K.} and Tan, {Timothy J.C.} and Narayanan, {Krishna K.} and Erik Procko",
note = "Acknowledgments: The Roy J. Carver Biotechnology Center at the University of Illinois assisted with flow cytometry and Illumina sequencing. Funding: This work was, in part, supported by NIH award R01AI129719 to E.P. Author contributions: E.P. designed the study and completed deep mutagenesis. K.K.C. purified proteins and tested BLI kinetics. K.K.C., K.K.N., and T.J.C.T. did flow cytometry. Competing interests: E.P. is an inventor on patent applications related to this work filed by the University of Illinois (number 62/989,976, filed 16 March 2020; number PCT/US2020/050903, filed 15 September 2020; number 63/089,895, filed 9 October 2020). E.P. and K.K.C. are cofounders of Orthogonal Biologics Inc. The authors declare that they have no other competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors.",
year = "2021",
month = feb,
day = "17",
doi = "10.1101/2020.10.18.344622",
language = "English (US)",
volume = "7",
journal = "Science advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "8",
}