Evidence map›Paper›PMID 36475798›Full record

ArticleScience advances2022

Optimized ACE2 decoys neutralize antibody-resistant SARS-CoV-2 variants through functional receptor mimicry and treat infection in vivo.

James A Torchia, Alexander H Tavares, Laura S Carstensen, Da-Yuan Chen, Jessie Huang, Tianshu Xiao, Sonia Mukherjee, Patrick M Reeves, Hua Tu, Ann E Sluder and 6 more

Open access · goldAbstract read
In one paragraph

Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.2field-weighted citation impact, top 10% of its field
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

16 citing papers in PubMed, 24 citations in OpenAlex.

  1. Review
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  7. Facilitating and restraining virus infection using cell-attachable soluble viral receptors.Proceedings of the National Academy of Sciences of the United States of America · 2024
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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 at 5 institutions in 1 country.

James A TorchiaDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA.ORCID 0000-0001-5291-8698
Alexander H TavaresNational Emerging Infectious Diseases Laboratories (NEIDL), Boston University, Boston, MA 02118, USA.ORCID 0000-0002-8363-4505
Laura S CarstensenDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA.ORCID 0000-0002-3410-281X
Da-Yuan ChenNational Emerging Infectious Diseases Laboratories (NEIDL), Boston University, Boston, MA 02118, USA.ORCID 0000-0002-1957-3330
Jessie HuangCenter for Regenerative Medicine of Boston University, Boston Medical Center, and The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.ORCID 0000-0002-5297-3563
Tianshu XiaoDivision of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0003-1287-1228
Sonia MukherjeeVaccine and Immunotherapy Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
Patrick M ReevesVaccine and Immunotherapy Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.ORCID 0000-0001-8202-0723
Hua TuLakePharma Inc., San Carlos, CA 94070, USA.
Ann E SluderVaccine and Immunotherapy Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.ORCID 0000-0003-4415-0652
Bing ChenDivision of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-8625-1657
Darrell N KottonCenter for Regenerative Medicine of Boston University, Boston Medical Center, and The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.ORCID 0000-0002-9604-8476
Richard A BowenDepartment of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
Mohsan SaeedNational Emerging Infectious Diseases Laboratories (NEIDL), Boston University, Boston, MA 02118, USA.ORCID 0000-0001-8505-7054
Mark C PoznanskyVaccine and Immunotherapy Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
Gordon J FreemanDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA.ORCID 0000-0002-7210-5616
Harvard University · USBoston Medical Center · USBoston University · USColorado State University · USLakePharma (United States) · US

Funding

Physician Scientist Training in Cancer ResearchT32CA009172 · NCI · DANA-FARBER CANCER INSTITUTE · PI Jennifer R Brown, James A. DeCaprio · 1985 to 2026
$17.1M
Structure-function studies of the membrane-interacting domains of HIV-1 Env spikeR01AI127193 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI CHEN, BING, HARRISON, STEPHEN COPLAN · 2016 to 2025
$8.4M
Derivation of Transplantable Lung Epithelial Progenitors from iPS CellsR01HL095993 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI Darrell N. Kotton · 2009 to 2026
$7.5M
A National iPS Cell Network with Deep Phenotyping for Translational ResearchU01TR001810 · NCATS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI GILAD, YOAV, KOTTON, DARRELL N. · 2016 to 2020
$4.4M
Structure of the full-length spike protein of SARS-CoV-2 in the context of membraneR01AI147884 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI CHEN, BING · 2020 to 2024
$3.4M
NCATS NIH HHS U01 TR001810NCI NIH HHS T32 CA009172NHLBI NIH HHS R01 HL095993NIAID NIH HHS R01 AI127193NIAID NIH HHS R01 AI147884
6 · The paper itself

Abstract

As severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) evolves to escape natural antibodies, it also loses sensitivity to therapeutic antibody drugs. By contrast, evolution selects for binding to ACE2, the cell-surface receptor required for SARS-CoV-2 infection. Consistent with this, we find that an ACE2 decoy neutralizes antibody-resistant variants, including Omicron, with no loss in potency. To identify design features necessary for in vivo activity, we compare several enzymatically inactive, Fc effector-silenced ACE2-Fc decoys. Inclusion of the ACE2 collectrin-like domain not only improves affinity for the S protein but also unexpectedly extends serum half-life and is necessary to reduce disease severity and viral titer in Syrian hamsters. Fc effector function is not required. The activity of ACE2 decoy receptors is due, in part, to their ability to trigger an irreversible structural change in the viral S protein. Our studies provide a new understanding of how ACE2 decoys function and support their development as therapeutics to treat ACE2-dependent coronaviruses.

Indexed as

COVID-19SARS-CoV-2Humans

Identifiers

PMID36475798
PMCPMC9728973
OpenAlexW4311589775

What OpenQuestion holds

Textmetadata
LicenceCC BY
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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.