ACE2-like carboxypeptidase B38-CAP protects from SARS-CoV-2-induced lung injury
Bibliographic record
Abstract
Abstract 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 (Ang II) to angiotensin 1-7 (Ang 1-7) and thereby improves the pathologies of cardiovascular disease or acute lung injury. To address whether the carboxypeptidase activity of ACE2 is protective in COVID-19, we investigated the effects of B38-CAP, an ACE2-like enzyme, on SARS-CoV-2-induced lung injury. Expression of endogenous ACE2 protein was significantly downregulated in the lungs of SARS-CoV-2-infected hamsters or SARS-CoV-2 challenged human ACE2 transgenic mice, leading to elevation of Ang II levels. In vivo administration of recombinant SARS-CoV-2 Spike also downregulated ACE2 expression, elevated Ang II levels and considerably worsened the symptoms of acute lung injury in hamsters exposed to acid aspiration. Despite its ACE2-like catalytic core, B38-CAP neither bound to Spike nor neutralized cell entry of SARS-CoV-2. However, treatment with B38-CAP improved the pathologies of Spike-augmented acid-induced lung injury. In SARS-CoV-2-infected hamsters, B38-CAP significantly improved lung edema and pathologies of lung injury and downregulated IL-6 levels without affecting viral RNA loads. Moreover, in human ACE2 transgenic mice, B38-CAP also attenuated SARS-CoV-2-induced lung edema and pathologies and improved lung functions. These results provide the first experimental in vivo evidence that increasing ACE2-like enzymatic activity is a potential therapeutic strategy to alleviate lung pathologies in COVID-19.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".