Evidence map›Paper›PMID 40276779›Full record

ArticleMolecular therapy. Methods & clinical development2025

Engineered ACE2 decoy in dry powder form for inhalation: A novel therapy for SARS-CoV-2 variants.

Takaaki Ito, Tatsuya Suzuki, Yusuke Sakai, Keisuke Nishioka, Yumi Itoh, Kentarou Sakamoto, Nariko Ikemura, Satoaki Matoba, Yasunari Kanda, Junichi Takagi and 3 more

Abstract read
In one paragraph

Article in Molecular therapy. Methods & clinical development, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

13 authors.

Takaaki ItoLaboratory of Pharmaceutical Engineering, Gifu Pharmaceutical University, Gifu 501-1196, Japan.
Tatsuya SuzukiDepartment of Microbiology, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
Yusuke SakaiDepartment of Pathology, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
Keisuke NishiokaDepartment of Infectious Diseases, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
Yumi ItohDepartment of Microbiology, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
Kentarou SakamotoLaboratory for Protein Synthesis and Expression, Institute for Protein Research, Osaka University, Osaka 565-0871, Japan.
Nariko IkemuraDepartment of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
Satoaki MatobaDepartment of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
Yasunari KandaDivision of Pharmacology, National Institute of Health Sciences, Kanagawa 210-9501, Japan.
Junichi TakagiLaboratory for Protein Synthesis and Expression, Institute for Protein Research, Osaka University, Osaka 565-0871, Japan.
Toru OkamotoDepartment of Microbiology, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
Kohei TaharaLaboratory of Pharmaceutical Engineering, Gifu Pharmaceutical University, Gifu 501-1196, Japan.
Atsushi HoshinoDepartment of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The persistent threat of SARS-CoV-2 and the emergence of new variants has prompted the development of a novel, easily administered modality that can overcome viral mutations. The engineered ACE2 decoy shows neutralizing activity comparable to monoclonal antibodies and is broadly effective against SARS-CoV-2 variants and ACE2-utilizing sarbecoviruses. In addition to intravenous administration, this decoy has shown antiviral efficacy through nebulized aerosol inhalation in murine and primate models, offering a dose-sparing advantage. Clinically, dry powder formulation is ideal for convenience and storage but poses challenges for protein biologics. This study developed a freeze-dried spray formulation of the ACE2 decoy for inhalation. The trehalose and leucine-based excipient maintained neutralizing activity and prevented aggregate formation. The dry powder showed aerodynamic distribution from bronchi to alveoli, aiding protection against SARS-CoV-2 infections. Neutralizing activity, structural stability, and powder dispersibility were preserved after 6 months of storage. In a mouse model of SARS-CoV-2 infection, significant reductions in viral replication and lung pathology were observed with intratracheal administration 24 h post-infection. The ACE2 decoy retained activity against recent JN.1 and current KP.3 strains, confirming its robust efficacy against viral mutations. This ACE2 decoy powder inhalant is a self-administered, next-generation treatment addressing the ongoing immune-evading evolution of SARS-CoV-2.

Indexed as

ACE2 decoydry powder formulationescape mutationsSARS-CoV-2variants

Identifiers

PMID40276779
PMCPMC12019485

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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.