Evidence map›Paper›PMID 40450691›Full record

ArticleCell reports2025

Designed miniproteins potently inhibit and protect against MERS-CoV.

Robert J Ragotte, M Alejandra Tortorici, Nicholas J Catanzaro, Amin Addetia, Brian Coventry, Heather M Froggatt, Jimin Lee, Cameron Stewart, Jack T Brown, Inna Goreshnik and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 citing papers in PubMed.

  1. Article
  2. Article
  3. Scalable Production of aPharmaceutics · 2026
    Article
  4. Article
  5. Computational design of an ultrapotent deltacoronavirus miniprotein inhibitor.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  6. Review
  7. Miniprotein inhibitors of thebioRxiv : the preprint server for biology · 2026
    Article
  8. Review
  9. Protein engineering: status report.Protein engineering, design & selection : PEDS · 2026
    Review
  10. Article
  11. Review
  12. Article
  13. Design of high specificity binders for peptide-MHC-I complexes.bioRxiv : the preprint server for biology · 2024
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors.

Robert J RagotteDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
M Alejandra TortoriciDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Nicholas J CatanzaroDepartment of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA.
Amin AddetiaDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Brian CoventryDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Heather M FroggattDepartment of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA.
Jimin LeeDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Cameron StewartDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Jack T BrownDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Inna GoreshnikDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Jeremiah N SimsDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Lukas F MillesDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Basile I M WickyDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Matthias GlöglDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Stacey GerbenDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Alex KangDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Asim K BeraDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
William SharkeyDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Alexandra SchäferDepartment of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA.
Jack R HarkemaDepartment of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, USA.
Ralph S BaricDepartment of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA. Electronic address: rbaric@email.unc.edu.
David BakerDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA; Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA. Electronic address: dabaker@uw.edu.
David VeeslerDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA. Electronic address: dveesler@uw.edu.

Funding

Research Project 1: Coronavirus antiviral lead development and combination testingU19AI171292 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HEISE, MARK T · 2022 to 2022
$65.5M
Centers for Research on Structural Biology of Infectious Diseases: Universal Influenza Vaccine Research75N93022C00036 · NIAID · SEATTLE CHILDREN'S HOSPITAL · PI STAKER, BART · 2022 to 2025
$21.7M
Structure-based design of broadly protective coronavirus vaccinesP01AI167966 · NIAID · UNIVERSITY OF WASHINGTON · PI Francois J Villinger · 2022 to 2026
$15.3M
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
De Novo Design of Minibinder Antagonists for COVID-19 and Future PandemicsR01AI160052 · NIAID · UNIVERSITY OF WASHINGTON · PI BAKER, DAVID, FULLER, DEBORAH H. · 2021 to 2025
$3.5M
Acquisition of a high resolution, high throughput cryo-electron microscopeS10OD023476 · OD · UNIVERSITY OF WASHINGTON · PI KOLLMAN, JUSTIN M · 2017 to 2017
$2.0M
Howard Hughes Medical InstituteNIAID NIH HHS 75N93022C00036NIAID NIH HHS DP1 AI158186NIAID NIH HHS P01 AI167966NIAID NIH HHS R01 AI160052NIAID NIH HHS U19 AI171292NIH HHS S10 OD023476
6 · The paper itself

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic pathogen with a 36% case-fatality rate in humans. No vaccines or specific therapeutics are currently approved for use in humans or the camel host reservoir. Here, we computationally designed monomeric and homo-oligomeric miniproteins that bind with high affinity to the MERS-CoV spike (S) glycoprotein, the main target of neutralizing antibodies and vaccine development. We show that these miniproteins broadly neutralize a panel of MERS-CoV S variants, spanning the known antigenic diversity of this pathogen, by targeting a conserved site in the receptor-binding domain (RBD). The miniproteins directly compete with binding of the dipeptidylpeptidase 4 (DPP4) receptor to MERS-CoV S, thereby blocking viral attachment to the host entry receptor and subsequent membrane fusion. Intranasal administration of a lead miniprotein provides prophylactic protection against stringent MERS-CoV challenge in mice, motivating its future clinical development as a next-generation countermeasure against this virus with pandemic potential.

Indexed as

Coronavirus InfectionsMiddle East Respiratory Syndrome CoronavirusAnimalsAntibodies, NeutralizingAntibodies, ViralDipeptidyl Peptidase 4FemaleHumansMiceProtein BindingSpike Glycoprotein, CoronavirusAntibodies, NeutralizingAntibodies, ViralDipeptidyl Peptidase 4Spike Glycoprotein, CoronaviruscoronavirusesCP: Immunologycryo-EMfusion assaysMERS-CoVminiproteinsprotein designspike glycoproteintherapeuticsVSV-neutralizationX-ray crystallography

Identifiers

PMID40450691
PMCPMC12276895

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Registered trials

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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.