Evidence map›Paper›PMID 34155214›Full record

ArticleNature communications2021

Engineered ACE2 receptor therapy overcomes mutational escape of SARS-CoV-2.

Yusuke Higuchi, Tatsuya Suzuki, Takao Arimori, Nariko Ikemura, Emiko Mihara, Yuhei Kirita, Eriko Ohgitani, Osam Mazda, Daisuke Motooka, Shota Nakamura and 8 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.

0numbers the graph read from it
0cells of the map it votes in
89citing papers in PubMed
8.2field-weighted citation impact, top 2% 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

89 citing papers in PubMed, 144 citations in OpenAlex.

  1. Review
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  15. Molecular therapy. Nucleic acids · 2025
    Article
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29 more citing papers are in PubMed but not listed here.

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

18 authors at 4 institutions in 1 country.

Yusuke Higuchi *Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Tatsuya Suzuki *Institute for Advanced Co-Creation Studies, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Takao Arimori *Laboratory for Protein Synthesis and Expression, Institute for Protein Research, Osaka University, Osaka, Japan.ORCID 0000-0002-6063-5572
Nariko Ikemura *Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Emiko MiharaLaboratory for Protein Synthesis and Expression, Institute for Protein Research, Osaka University, Osaka, Japan.ORCID 0000-0002-9127-8643
Yuhei KiritaDepartment of Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.ORCID 0000-0002-5240-5531
Eriko OhgitaniDepartment of Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Osam MazdaDepartment of Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.ORCID 0000-0001-9489-3556
Daisuke MotookaDepartment of Infection Metagenomics, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Shota NakamuraDepartment of Infection Metagenomics, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Yusuke SakaiDepartment of Veterinary Pathology, Yamaguchi University, Yamaguchi, Japan.ORCID 0000-0003-0531-8256
Yumi ItohInstitute for Advanced Co-Creation Studies, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Fuminori SugiharaThe Core Instrumentation Facility, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Yoshiharu MatsuuraDepartment of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.ORCID 0000-0001-9091-8285
Satoaki MatobaDepartment of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.ORCID 0000-0002-9373-4331
Toru OkamotoInstitute for Advanced Co-Creation Studies, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan. toru@biken.osaka-u.ac.jp.ORCID 0000-0003-4000-3102
Junichi TakagiLaboratory for Protein Synthesis and Expression, Institute for Protein Research, Osaka University, Osaka, Japan. takagi@protein.osaka-u.ac.jp.ORCID 0000-0002-1219-475X
Atsushi HoshinoDepartment of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. a-hoshi@koto.kpu-m.ac.jp.ORCID 0000-0002-4015-1319
Kyoto Prefectural University of Medicine · JPThe University of Osaka · JPProtein Research Foundation · JPYamaguchi University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

SARS-CoV-2 has mutated during the global pandemic leading to viral adaptation to medications and vaccinations. Here we describe an engineered human virus receptor, ACE2, by mutagenesis and screening for binding to the receptor binding domain (RBD). Three cycles of random mutagenesis and cell sorting achieved sub-nanomolar affinity to RBD. Our structural data show that the enhanced affinity comes from better hydrophobic packing and hydrogen-bonding geometry at the interface. Additional disulfide mutations caused the fixing of a closed ACE2 conformation to avoid off-target effects of protease activity, and also improved structural stability. Our engineered ACE2 neutralized SARS-CoV-2 at a 100-fold lower concentration than wild type; we also report that no escape mutants emerged in the co-incubation after 15 passages. Therapeutic administration of engineered ACE2 protected hamsters from SARS-CoV-2 infection, decreased lung virus titers and pathology. Our results provide evidence of a therapeutic potential of engineered ACE2.

Indexed as

COVID-19 Drug TreatmentMutationAngiotensin-Converting Enzyme 2AnimalsCells, CulturedCOVID-19CricetinaeCrystallography, X-RayDisease Models, AnimalHumansMaleMolecular Dynamics SimulationProtein BindingProtein EngineeringSARS-CoV-2Spike Glycoprotein, CoronavirusACE2 protein, humanAngiotensin-Converting Enzyme 2Spike Glycoprotein, Coronavirus

Identifiers

PMID34155214
PMCPMC8217473
OpenAlexW3176022402

What OpenQuestion 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 OpenQuestion graph.