Evidence map›Paper›PMID 41256381›Full record

ArticlebioRxiv : the preprint server for biology2025

Directed evolution of a stem-helix-targeting antibody enables MERS-CoV cross-neutralization through enhanced binding affinity.

Panpan Zhou, Meng Yuan, Yuexiu Zhang, Oliver Limbo, Ge Song, Fangzhu Zhao, Hejun Liu, Wan-Ting He, Tazio Capozzola, Sean Callaghan and 10 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. 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

20 authors.

Panpan ZhouDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Meng YuanDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.ORCID 0000-0001-9754-4503
Yuexiu ZhangDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Oliver LimboDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Ge SongDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Fangzhu ZhaoDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Hejun LiuDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Wan-Ting HeDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Tazio CapozzolaDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Sean CallaghanDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Gabriel AvillionDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Xuduo LiDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Nathan BeutlerDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Peter YongDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Fabio AnzanelloDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Thomas F RogersDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Dennis R BurtonDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Joseph G JardineDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Ian A WilsonConsortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
Raiees AndrabiDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Funding

A Synchrotron Radiation Structural Biology ResourcesP30GM133894 · NIGMS · STANFORD UNIVERSITY · PI Aina E. Cohen, KEITH O HODGSON · 2020 to 2026
$43.3M
User Training & OutreachP30GM138396 · NIGMS · UCHICAGO ARGONNE, LLC · PI ROBERT F. FISCHETTI, JANET L. SMITH · 2020 to 2026
$34.3M
Development of pan-betacoronavirus vaccinesR01AI170928 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Raiees Ahmad Andrabi · 2023 to 2026
$3.0M
Novel B cell epitope discovery against human coronavirusesR01AI190286 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI IAN A WILSON · 2025 to 2026
$1.8M
Gates Foundation INV-004923NIAID NIH HHS R01 AI170928NIAID NIH HHS R01 AI190286NIGMS NIH HHS P30 GM133894NIGMS NIH HHS P30 GM138396
6 · The paper itself

Abstract

Broadly neutralizing antibodies (bnAbs) targeting conserved regions of the betacoronavirus spike are important for pan-betacoronavirus protection and pandemic preparedness. Here, we report on the isolation of a human monoclonal antibody, CC65.1, from a SARS-CoV-2 convalescent donor that targets the conserved S2 stem helix region. CC65.1 neutralizes various sarbecoviruses, including SARS-CoV-2, and binds the MERS-CoV spike but lacks MERS-CoV-neutralizing activity due to insufficient binding affinity. We utilized directed evolution to enhance the binding affinity of CC65.1 for the MERS-CoV S2 stem helix, yielding engineered antibody variants with newly acquired MERS-CoV-neutralizing activity. High-resolution structural analysis reveals key paratope mutations that optimize binding and stabilize epitope engagement. Our findings demonstrate the potential of rational antibody engineering to expand bnAb breadth across divergent betacoronaviruses. This work supports the development of engineered bnAbs and S2-targeted vaccines for broad betacoronavirus countermeasures and highlights strategies to achieve cross-lineage immunity for future pandemic threats.

Identifiers

PMID41256381
PMCPMC12621793

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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.