Evidence map›Paper›PMID 41318533›Full record

ArticleNature communications2025

Development of ACE2-tropic-betacoronavirus therapeutics for future pandemic preparedness.

Ashley Utz, Matt Armbrust, Thuy-Tien T Nguyen, Mary Kate Morris, Chris O Matthews, Pallavi Kompella, Zheng Cao, Ji Won Ha, Arvie Violette, R Camille Brewer and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 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

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Ashley UtzStanford Biophysics Program, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-2280-8521
Matt ArmbrustInnovative Medicines Accelerator, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-4701-806X
Thuy-Tien T NguyenSarafan ChEM-H, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-1676-733X
Mary Kate MorrisCenter for Laboratory Sciences, California Department of Public Health, Richmond, CA, USA.
Chris O MatthewsSarafan ChEM-H, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0009-0003-2058-4840
Pallavi KompellaInnovative Medicines Accelerator, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-9508-5603
Zheng CaoSarafan ChEM-H, Stanford University, Stanford, CA, USA.
Ji Won HaInnovative Medicines Accelerator, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-7782-9090
Arvie VioletteStanford Biophysics Program, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0009-0004-9561-8926
R Camille BrewerDivision of Immunology and Rheumatology, Stanford, CA, USA.
Tobias V LanzDivision of Immunology and Rheumatology, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-7106-8801
William H RobinsonDivision of Immunology and Rheumatology, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-4385-704X
Duo XuSarafan ChEM-H, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-0483-8719
Carl HansonCenter for Laboratory Sciences, California Department of Public Health, Richmond, CA, USA.
Adrian HugenmatterSarafan ChEM-H, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0009-0004-2757-5709
Peter S KimSarafan ChEM-H, Stanford University, Stanford, CA, USA. kimpeter@stanford.edu.ORCID http://orcid.org/0000-0001-6503-4541

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007365 · NIGMS · STANFORD UNIVERSITY · PI CHUA, KATRIN F · 1985 to 2021
$33.8M
Medical Scientist Training ProgramT32GM145402 · NIGMS · STANFORD UNIVERSITY · PI Katrin F. Chua · 2022 to 2026
$10.0M
Molecular Biophysics Training Program at StanfordT32GM136568 · NIGMS · STANFORD UNIVERSITY · PI Zev Bryant, KERWYN C. HUANG · 2021 to 2026
$3.7M
NIGMS NIH HHS T32 GM007365NIGMS NIH HHS T32 GM136568NIGMS NIH HHS T32 GM145402
6 · The paper itself

Abstract

A major challenge during viral pandemics is the ability to develop therapeutics whose efficacy can withstand viral genetic evolution. During the COVID-19 pandemic, five SARS-CoV-2 monoclonal antibody (mAb) therapeutics were rendered ineffective within a period of 2 years, leading to the U.S. FDA revoking their emergency use authorization. Here, we describe ReconnAb-multimers, a new therapeutic design that broadly and potently neutralize all tested betacoronaviruses that use host ACE2 as their receptor to enter cells. These ReconnAb-multimers have potent neutralization efficacy via avidity, enhanced breadth via a new pan-betacoronavirus-binding antibody that targets a highly conserved epitope on SARS-CoV-2 spike protein, and the potential for clinical development by using a catalytically inactive ACE2 component. We demonstrate that ReconnAb-multimers neutralize all SARS-CoV-2 pseudoviruses and authentic viral variants of concern (VOC) tested, with similar or higher potency than mAbs previously approved by the FDA; neutralize related pandemic-potential betacoronaviruses, including SARS-CoV, WIV1-CoV, PRD-0038, and merbecovirus HKU5-CoV-2; and despite a short half-life, protect female mice against authentic viral challenge with Omicron variant XBB.1.5. Our results highlight ReconnAb-multimers as a broad and highly potent therapeutic that could potentially withstand viral escape against current and future betacoronaviruses that require host ACE2 as a receptor.

Indexed as

Angiotensin-Converting Enzyme 2Antibodies, ViralCOVID-19COVID-19 Drug TreatmentSARS-CoV-2AnimalsAntibodies, MonoclonalAntibodies, NeutralizingFemaleHumansMicePandemic PreparednessPandemicsSpike Glycoprotein, CoronavirusACE2 protein, humanAngiotensin-Converting Enzyme 2Antibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2

Identifiers

PMID41318533
PMCPMC12775405

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.