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Record W3110699530 · doi:10.1038/s41467-021-27097-8

ACE2-like carboxypeptidase B38-CAP protects from SARS-CoV-2-induced lung injury

2021· article· en· W3110699530 on OpenAlexafffund
Tomokazu Yamaguchi, Midori Hoshizaki, Takafumi Minato, Satoru Nirasawa, Masamitsu N. Asaka, Mayumi Niiyama, Masaki Imai, Akihiko Uda, Jasper Fuk‐Woo Chan, Saori Takahashi, Jianbo An, Akari Saku, Ryota Nukiwa, Daichi Utsumi, Maki Kiso, Atsuhiro Yasuhara, Vincent Kwok‐Man Poon, Chris Chung‐Sing Chan, Yuji Fujino, Satoru Motoyama, Satoshi Nagata, Josef Penninger, Haruhiko Kamada, Kwok‐Yung Yuen, Wataru Kamitani, Ken Maeda, Yoshihiro Kawaoka, Yasuhiro Yasutomi, Yumiko Imai, Keiji Kuba

Bibliographic record

VenueNature Communications · 2021
Typearticle
Languageen
FieldMedicine
TopicCOVID-19 Clinical Research Studies
Canadian institutionsUniversity of British Columbia
FundersCanadian Institutes of Health ResearchInnovative Medicines InitiativeJapan Society for the Promotion of ScienceAustrian Science FundMinistry of Education, Culture, Sports, Science and TechnologyÖsterreichischen Akademie der WissenschaftenJapan Agency for Medical Research and DevelopmentNaito Foundation
KeywordsCoronavirus disease 2019 (COVID-19)Sars virusSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)CarboxypeptidaseMedicineVirology2019-20 coronavirus outbreakBetacoronavirusLungCoronavirus InfectionsBiologyPathologyEnzymeInternal medicineBiochemistry

Abstract

fetched live from OpenAlex

Angiotensin-converting enzyme 2 (ACE2) is a receptor for cell entry of SARS-CoV-2, and recombinant soluble ACE2 protein inhibits SARS-CoV-2 infection as a decoy. ACE2 is a carboxypeptidase that degrades angiotensin II, thereby improving the pathologies of cardiovascular disease or acute lung injury. Here we show that B38-CAP, an ACE2-like enzyme, is protective against SARS-CoV-2-induced lung injury. Endogenous ACE2 expression is downregulated in the lungs of SARS-CoV-2-infected hamsters, leading to elevation of angiotensin II levels. Recombinant Spike also downregulates ACE2 expression and worsens the symptoms of acid-induced lung injury. B38-CAP does not neutralize cell entry of SARS-CoV-2. However, B38-CAP treatment improves the pathologies of Spike-augmented acid-induced lung injury. In SARS-CoV-2-infected hamsters or human ACE2 transgenic mice, B38-CAP significantly improves lung edema and pathologies of lung injury. These results provide the first in vivo evidence that increasing ACE2-like enzymatic activity is a potential therapeutic strategy to alleviate lung pathologies in COVID-19 patients.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.030
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMetaresearch, Research integrity
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.732
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.030
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.002
Research integrity0.0010.004
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.080
GPT teacher head0.467
Teacher spread0.386 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations57
Published2021
Admission routes2
Has abstractyes

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