Evidence map›Paper›PMID 39574666›Full record

ArticlebioRxiv : the preprint server for biology2024

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 12 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. 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

22 authors.

Robert J RagotteDepartment of Biochemistry, 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.
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.
Jeremiah N SimsDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Lukas F MillesDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Basile I M WickyDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Matthias GlöglDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Stacey GerbenDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Alex KangDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Asim K BeraDepartment of Biochemistry, 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.
Ralph S BaricDepartment of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA.
David BakerDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
David VeeslerDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.

Funding

Research Project 1: Coronavirus antiviral lead development and combination testingU19AI171292 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI WILLSON, TIMOTHY M · 2022 to 2022
$65.5M
User Training and OutreachP30GM124165 · NIGMS · CORNELL UNIVERSITY · PI STEVEN E EALICK · 2018 to 2026
$34.2M
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 BALI PULENDRAN · 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
NIAID NIH HHS 75N93022C00036NIAID NIH HHS DP1 AI158186NIAID NIH HHS P01 AI167966NIAID NIH HHS R01 AI160052NIAID NIH HHS U19 AI171292NIGMS NIH HHS P30 GM124165
6 · The paper itself

Abstract

Middle-East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic pathogen with 36% case-fatality rate in humans. No vaccines or specific therapeutics are currently approved to use in humans or the camel host reservoir. Here, we computationally designed monomeric and homo-oligomeric miniproteins binding 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 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 future clinical development as a next-generation countermeasure against this virus with pandemic potential.

Identifiers

PMID39574666
PMCPMC11580849

What Socratic holds

Textmetadata
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 Socratic graph.