Evidence map›Paper›PMID 33154107›Full record

ArticleScience (New York, N.Y.)2020

De novo design of potent and resilient hACE2 decoys to neutralize SARS-CoV-2.

Thomas W Linsky, Renan Vergara, Nuria Codina, Jorgen W Nelson, Matthew J Walker, Wen Su, Christopher O Barnes, Tien-Ying Hsiang, Katharina Esser-Nobis, Kevin Yu and 25 more

Open access · hybridAbstract read
In one paragraph

Article in Science (New York, N.Y.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers.

0numbers the graph read from it
0cells of the map it votes in
131citing papers in PubMed
4.7field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

131 citing papers in PubMed, 208 citations in OpenAlex.

  1. Review
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  8. Design and evolution of a synthetic small protein scaffold based on the WW domain.Protein science : a publication of the Protein Society · 2025
    Article
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  11. Review
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  17. Radiotracers for Molecular Imaging of Angiotensin-Converting Enzyme 2.International journal of molecular sciences · 2024
    Review
  18. Review
  19. Review
  20. Article

71 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

  • Update of
    2020
5 · Who and what money

Authors and funding

35 authors at 6 institutions in 2 countries.

Thomas W Linsky *Neoleukin Therapeutics Inc., Seattle, WA, USA.ORCID 0000-0002-1632-3395
Renan Vergara *Neoleukin Therapeutics Inc., Seattle, WA, USA.ORCID 0000-0002-3680-5105
Nuria Codina *Neoleukin Therapeutics Inc., Seattle, WA, USA.ORCID 0000-0003-3945-2242
Jorgen W Nelson *Neoleukin Therapeutics Inc., Seattle, WA, USA.ORCID 0000-0002-0202-2460
Matthew J WalkerNeoleukin Therapeutics Inc., Seattle, WA, USA.ORCID 0000-0001-5541-9245
Wen SuSchool of Public Health, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong Special Administrative Region, China.ORCID 0000-0002-2291-6349
Christopher O BarnesDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Tien-Ying HsiangCenter for Innate Immunity and Immune Disease, Department of Immunology, University of Washington, Seattle, WA, USA.ORCID 0000-0002-4316-4561
Katharina Esser-NobisCenter for Innate Immunity and Immune Disease, Department of Immunology, University of Washington, Seattle, WA, USA.ORCID 0000-0002-9027-0391
Kevin YuNeoleukin Therapeutics Inc., Seattle, WA, USA.ORCID 0000-0002-6725-0413
Z Beau ReneerCenter for Vaccines and Immunology, University of Georgia, Athens, GA, USA.ORCID 0000-0002-5685-000X
Yixuan J HouCenter for Innate Immunity and Immune Disease, Department of Immunology, University of Washington, Seattle, WA, USA.ORCID 0000-0002-8323-7243
Tanu PriyaNeoleukin Therapeutics Inc., Seattle, WA, USA.
Masaya MitsumotoNeoleukin Therapeutics Inc., Seattle, WA, USA.
Avery PongNeoleukin Therapeutics Inc., Seattle, WA, USA.
Uland Y LauNeoleukin Therapeutics Inc., Seattle, WA, USA.ORCID 0000-0002-4758-6884
Marsha L MasonNeoleukin Therapeutics Inc., Seattle, WA, USA.ORCID 0000-0002-8968-2196
Jerry ChenNeoleukin Therapeutics Inc., Seattle, WA, USA.ORCID 0000-0001-5276-6735
Alex ChenNeoleukin Therapeutics Inc., Seattle, WA, USA.
Tania BerrocalNeoleukin Therapeutics Inc., Seattle, WA, USA.ORCID 0000-0002-9411-9197
Hong PengNeoleukin Therapeutics Inc., Seattle, WA, USA.
Nicole S ClairmontNeoleukin Therapeutics Inc., Seattle, WA, USA.
Javier CastellanosNeoleukin Therapeutics Inc., Seattle, WA, USA.
Yu-Ru LinNeoleukin Therapeutics Inc., Seattle, WA, USA.
Anna Josephson-DayNeoleukin Therapeutics Inc., Seattle, WA, USA.ORCID 0000-0003-4136-1622
Ralph S BaricDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID 0000-0001-6827-8701
Deborah H FullerDepartment of Microbiology, University of Washington, Seattle, WA, USA.ORCID 0000-0001-7315-2441
Carl D WalkeyNeoleukin Therapeutics Inc., Seattle, WA, USA.
Ted M RossCenter for Vaccines and Immunology, University of Georgia, Athens, GA, USA.
Ryan SwansonNeoleukin Therapeutics Inc., Seattle, WA, USA.ORCID 0000-0003-3403-3591
Pamela J BjorkmanDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.ORCID 0000-0002-2277-3990
Michael GaleCenter for Innate Immunity and Immune Disease, Department of Immunology, University of Washington, Seattle, WA, USA.ORCID 0000-0002-6332-7436
Luis M Blancas-MejiaNeoleukin Therapeutics Inc., Seattle, WA, USA.ORCID 0000-0002-2516-2482
Hui-Ling YenSchool of Public Health, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong Special Administrative Region, China.ORCID 0000-0003-2493-3609
Daniel-Adriano SilvaNeoleukin Therapeutics Inc., Seattle, WA, USA. dadriano@neoleukin.com.ORCID 0000-0002-3195-9009
Neoleukin Therapeutics (United States) · USUniversity of Washington · USCalifornia Institute of Technology · USUniversity of Georgia · USUniversity of Hong Kong · HKUniversity of North Carolina at Chapel Hill · US

Funding

Virus TransmissionP50AI150464 · NIAID · UNIVERSITY OF UTAH · PI SUNDQUIST, WESLEY I. · 2019 to 2021
$14.9M
Determinants of Coronavirus Fidelity in Replication and PathogenesisR01AI108197 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BARIC, RALPH S, DENISON, MARK R · 2013 to 2022
$6.5M
Receptor recognition mechanisms of coronavirusesR01AI089728 · NIAID · UNIVERSITY OF MINNESOTA · PI Fang Li, Timothy Patrick Sheahan · 2010 to 2026
$4.7M
Innate Immune Regulation of Zika Virus InfectionR01AI145296 · NIAID · UNIVERSITY OF WASHINGTON · PI COYNE, CAROLYN B, DIAMOND, MICHAEL S · 2019 to 2023
$4.1M
Mechanisms of hepatic innate immune activation by HCVR01AI127463 · NIAID · UNIVERSITY OF WASHINGTON · PI GALE, MICHAEL, ROSEN, HUGO RAMON · 2017 to 2021
$2.8M
Howard Hughes Medical InstituteNIAID NIH HHS HHSN272201400006CNIAID NIH HHS P50 AI150464NIAID NIH HHS R01 AI089728NIAID NIH HHS R01 AI108197NIAID NIH HHS R01 AI127463NIAID NIH HHS R01 AI145296
6 · The paper itself

Abstract

We developed a de novo protein design strategy to swiftly engineer decoys for neutralizing pathogens that exploit extracellular host proteins to infect the cell. Our pipeline allowed the design, validation, and optimization of de novo human angiotensin-converting enzyme 2 (hACE2) decoys to neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The best monovalent decoy, CTC-445.2, bound with low nanomolar affinity and high specificity to the receptor-binding domain (RBD) of the spike protein. Cryo-electron microscopy (cryo-EM) showed that the design is accurate and can simultaneously bind to all three RBDs of a single spike protein. Because the decoy replicates the spike protein target interface in hACE2, it is intrinsically resilient to viral mutational escape. A bivalent decoy, CTC-445.2d, showed ~10-fold improvement in binding. CTC-445.2d potently neutralized SARS-CoV-2 infection of cells in vitro, and a single intranasal prophylactic dose of decoy protected Syrian hamsters from a subsequent lethal SARS-CoV-2 challenge.

Indexed as

COVID-19 Drug TreatmentAngiotensin-Converting Enzyme 2AnimalsAntiviral AgentsCricetinaeCryoelectron MicroscopyDirected Molecular EvolutionProtein BindingProtein DomainsProtein EngineeringReceptors, VirusRecombinant ProteinsSARS-CoV-2Spike Glycoprotein, CoronavirusAngiotensin-Converting Enzyme 2Antiviral AgentsReceptors, VirusRecombinant ProteinsSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2

Identifiers

PMID33154107
PMCPMC7920261
OpenAlexW3096331199

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.