Evidence map›Paper›PMID 34268509›Full record

ArticlebioRxiv : the preprint server for biology2021

Multivalent designed proteins protect against SARS-CoV-2 variants of concern.

Andrew C Hunt, James Brett Case, Young-Jun Park, Longxing Cao, Kejia Wu, Alexandra C Walls, Zhuoming Liu, John E Bowen, Hsien-Wei Yeh, Shally Saini and 36 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

46 authors.

Andrew C Hunt *Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL, 60208, USA.
James Brett Case *Department of Medicine, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Young-Jun Park *Department of Biochemistry, University of Washington, Seattle, WA, 98195, USA.
Longxing Cao *Department of Biochemistry, University of Washington, Seattle, WA, 98195, USA.
Kejia Wu *Department of Biochemistry, University of Washington, Seattle, WA, 98195, USA.
Alexandra C Walls *Department of Biochemistry, University of Washington, Seattle, WA, 98195, USA.
Zhuoming LiuDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
John E BowenDepartment of Biochemistry, University of Washington, Seattle, WA, 98195, USA.
Hsien-Wei YehDepartment of Biochemistry, University of Washington, Seattle, WA, 98195, USA.
Shally SainiDepartment of Biochemistry, University of Washington, Seattle, WA, 98195, USA.
Louisa HelmsDivision of Nephrology and Kidney Research Institute, Department of Medicine, University of Washington School of Medicine, Seattle, WA, 98109, USA.
Yan Ting ZhaoDepartment of Biochemistry, University of Washington, Seattle, WA, 98195, USA.
Tien-Ying HsiangDepartment of Immunology, Center for Innate Immunity and Immune Disease, University of Washington, Seattle, WA, 98195, USA.
Tyler N StarrBasic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.
Inna GoreshnikDepartment of Biochemistry, University of Washington, Seattle, WA, 98195, USA.
Lisa KozodoyDepartment of Biochemistry, University of Washington, Seattle, WA, 98195, USA.
Lauren CarterDepartment of Biochemistry, University of Washington, Seattle, WA, 98195, USA.
Rashmi RavichandranDepartment of Biochemistry, University of Washington, Seattle, WA, 98195, USA.
Lydia B GreenAmgen Research, Biologic Discovery, Burnaby, BC, Canada.
Wadim L MatochkoAmgen Research, Biologic Discovery, Burnaby, BC, Canada.
Christy A ThomsonAmgen Research, Biologic Discovery, Burnaby, BC, Canada.
Bastain VögeliDepartment of Chemical and Biological Engineering, Northwestern University, Evanston, IL, 60208, USA.
Antje Krüger-GerickeDepartment of Chemical and Biological Engineering, Northwestern University, Evanston, IL, 60208, USA.
Laura A VanBlarganDepartment of Medicine, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Rita E ChenDepartment of Medicine, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Baoling YingDepartment of Medicine, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Adam L BaileyDepartment of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Natasha M KafaiDepartment of Medicine, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Scott BoykenDepartment of Biochemistry, University of Washington, Seattle, WA, 98195, USA.
Ajasja LjubetičDepartment of Biochemistry, University of Washington, Seattle, WA, 98195, USA.
Natasha EdmanDepartment of Biochemistry, University of Washington, Seattle, WA, 98195, USA.
George UedaDepartment of Biochemistry, University of Washington, Seattle, WA, 98195, USA.
Cameron ChowDepartment of Biochemistry, University of Washington, Seattle, WA, 98195, USA.
Amin AddetiaDepartment of Biochemistry, University of Washington, Seattle, WA, 98195, USA.
Nuttada PanpradistDepartment of Bioengineering, University of Washington, Seattle, WA, 98195, USA.
Michael GaleDepartment of Immunology, Center for Innate Immunity and Immune Disease, University of Washington, Seattle, WA, 98195, USA.
Benjamin S FreedmanDivision of Nephrology and Kidney Research Institute, Department of Medicine, University of Washington School of Medicine, Seattle, WA, 98109, USA.
Barry R LutzDepartment of Bioengineering, University of Washington, Seattle, WA, 98195, USA.
Jesse D BloomBasic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.
Hannele Ruohola-BakerDepartment of Biochemistry, University of Washington, Seattle, WA, 98195, USA.
Sean P J WhelanDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Lance StewartDepartment of Biochemistry, University of Washington, Seattle, WA, 98195, USA.
Michael S DiamondDepartment of Medicine, Washington University School of Medicine, St. Louis, MO, 63110, USA.
David VeeslerDepartment of Biochemistry, University of Washington, Seattle, WA, 98195, USA.
Michael C JewettDepartment of Chemical and Biological Engineering, Northwestern University, Evanston, IL, 60208, USA.
David BakerDepartment of Biochemistry, University of Washington, Seattle, WA, 98195, USA.

Funding

Progenitor Cell Biology Consortium Administrative Coordinating CenterU01HL099997 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI TERRIN, MICHAEL L · 2009 to 2015
$29.9M
Self Renewal and Differentiation of Human Embryonic Stem CellsP01GM081619 · NIGMS · UNIVERSITY OF WASHINGTON · PI WARE, CAROL B · 2007 to 2017
$20.6M
University of Washington Arboviral Research Network (UWARN)U01AI151698 · NIAID · UNIVERSITY OF WASHINGTON · PI Michael Gale, PETER MACGARR RABINOWITZ · 2020 to 2026
$13.3M
Controlling Hematopoietic Lineage Commitment from ESC to PlateletsU01HL099993 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI TOROK-STORB, BEVERLY J. · 2009 to 2015
$8.3M
Human antibody-based countermeasures against the Wuhan Coronavirus SARS-CoV-2R01AI157155 · NIAID · WASHINGTON UNIVERSITY · PI BARIC, RALPH S, CROWE, JAMES E · 2020 to 2024
$6.0M
V-OLA: point-of-care HIV viral load monitoring and drug resistance testingR01AI145486 · NIAID · UNIVERSITY OF WASHINGTON · PI Barry Ryan Lutz · 2019 to 2026
$5.6M
Unraveling the bat humoral immune response against zoonotic viruses to guide the design of next-generation therapeuticsDP1AI158186 · NIAID · UNIVERSITY OF WASHINGTON · PI VEESLER, DAVID · 2020 to 2024
$5.4M
JAK-STAT Control of Zika Virus-Induced Fetal InjuryR01AI143265 · NIAID · UNIVERSITY OF WASHINGTON · PI ADAMS WALDORF, KRISTINA M., GALE, MICHAEL · 2019 to 2023
$4.6M
Tissue Chip Data to the Microphysiology Systems Database (MPS-Db) Supplement to A Microphysiological System for Kidney Disease Modeling and Drug Efficacy TestingUH3TR002158 · NCATS · UNIVERSITY OF WASHINGTON · PI HIMMELFARB, JONATHAN · 2019 to 2021
$4.2M
Innate Immune Regulation of Zika Virus InfectionR01AI145296 · NIAID · UNIVERSITY OF WASHINGTON · PI COYNE, CAROLYN B, DIAMOND, MICHAEL S · 2019 to 2023
$4.1M
A Microphysiological System for Kidney Disease Modeling and Drug Efficacy TestingUG3TR002158 · NCATS · UNIVERSITY OF WASHINGTON · PI HIMMELFARB, JONATHAN · 2017 to 2018
$2.9M
A Human Organoid Model of Polycystic Kidney DiseaseR01DK117914 · NIDDK · UNIVERSITY OF WASHINGTON · PI FREEDMAN, BENJAMIN SOLOMON · 2018 to 2022
$1.8M
NCATS NIH HHS UG3 TR002158NCATS NIH HHS UH3 TR002158NHLBI NIH HHS U01 HL099993NHLBI NIH HHS U01 HL099997NIAID NIH HHS DP1 AI158186NIAID NIH HHS HHSN272201700059CNIAID NIH HHS R01 AI143265NIAID NIH HHS R01 AI145296NIAID NIH HHS R01 AI145486NIAID NIH HHS R01 AI157155NIAID NIH HHS U01 AI151698NIDDK NIH HHS R01 DK117914NIGMS NIH HHS P01 GM081619NIGMS NIH HHS R01 GM083867NIGMS NIH HHS R01 GM097372NIGMS NIH HHS R01 GM120553
6 · The paper itself

Abstract

Escape variants of SARS-CoV-2 are threatening to prolong the COVID-19 pandemic. To address this challenge, we developed multivalent protein-based minibinders as potential prophylactic and therapeutic agents. Homotrimers of single minibinders and fusions of three distinct minibinders were designed to geometrically match the SARS-CoV-2 spike (S) trimer architecture and were optimized by cell-free expression and found to exhibit virtually no measurable dissociation upon binding. Cryo-electron microscopy (cryoEM) showed that these trivalent minibinders engage all three receptor binding domains on a single S trimer. The top candidates neutralize SARS-CoV-2 variants of concern with IC ONE-SENTENCE SUMMARY: We designed, developed, and characterized potent, trivalent miniprotein binders that provide prophylactic and therapeutic protection against emerging SARS-CoV-2 variants of concern.

Identifiers

PMID34268509
PMCPMC8282097

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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.