An engineered decoy receptor for SARS-CoV-2 broadly binds protein S sequence variants.

Science Advances
Kui K ChanErik Procko

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, sACE22v2.4, 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.

References

Mar 26, 2005·The EMBO Journal·Wenhui LiMichael Farzan
Oct 19, 2011·Bioinformatics·Douglas M FowlerStanley Fields
Feb 1, 2012·The Journal of Biological Chemistry·Kailang WuFang Li
Jul 6, 2013·Journal of Molecular Biology·Erik ProckoDavid Baker
Apr 30, 2014·Nature Reviews. Cardiology·Fan JiangCheng Zhang
Jul 31, 2014·Nature Methods·Douglas M Fowler, Stanley Fields
Feb 25, 2015·Nature·Matthew R GardnerMichael Farzan
Mar 26, 2016·Trends in Microbiology·Shuo SuGeorge F Gao
Apr 22, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jeremiah D HerediaErik Procko
Feb 7, 2019·The Journal of Biological Chemistry·Jihye ParkErik Procko
May 10, 2019·Journal of Virology·Christoph H FellingerMichael Farzan
Feb 23, 2020·Science·Daniel WrappJason S McLellan
Apr 1, 2020·Nature·Jian ShangFang Li
Apr 26, 2020·Nature Communications·Changhai LeiShi Hu
Jun 9, 2020·BioRxiv : the Preprint Server for Biology·Hannah K FrankScott D Boyd
Jun 26, 2020·Frontiers in Cellular and Infection Microbiology·Lobelia Samavati, Bruce D Uhal
Jun 27, 2020·BioRxiv : the Preprint Server for Biology·Lizhou ZhangHyeryun Choe
Jul 23, 2020·Science·Yongfei CaiBing Chen
Jul 24, 2020·Nature Structural & Molecular Biology·Rory HendersonPriyamvada Acharya
Jul 25, 2020·Science·Darlan S CandidoNuno Rodrigues Faria
Sep 11, 2020·Science·Longxing CaoDavid Baker
Sep 17, 2020·BioRxiv : the Preprint Server for Biology·Allison J GreaneyJesse D Bloom
Sep 28, 2020·Cell·Hangping YaoSai Li
Oct 24, 2020·Proceedings of the National Academy of Sciences of the United States of America·Anum GlasgowJames A Wells
Nov 3, 2020·The Lancet. Respiratory Medicine·Alexander ZoufalyJosef M Penninger
Nov 7, 2020·Science·Thomas W LinskyDaniel-Adriano Silva
Nov 12, 2020·Science·Bas B Oude MunninkMarion P G Koopmans
Mar 25, 2021·BioRxiv : the Preprint Server for Biology·David VanInsbergheKatia Koelle
Sep 16, 2020·BioRxiv : the Preprint Server for Biology·Y. HiguchiAtsushi Hoshino

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Citations

Apr 27, 2021·Frontiers in Molecular Biosciences·Krishna K Narayanan, Erik Procko
Mar 27, 2021·Nature·Erik VolzNeil M Ferguson
May 12, 2021·Proteins·Wenyang Jing, Erik Procko
Jun 22, 2021·Emerging Infectious Diseases·Welmoed van LoonFrank P Mockenhaupt

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Datasets Mentioned

BETA
KY432415.1
AAP13441.1
161821-161826
GSE159372

Methods Mentioned

BETA
biolayer interferometry
biosensors
flow cytometry
fluorescence-activated cell sorting
FACS
transfection
Illumina sequencing
PCR
FCS

Clinical Trials Mentioned

NCT04427501

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