ACE2-like carboxypeptidase B38-CAP protects from SARS-CoV-2-induced lung injury.
Nat Commun
; 12(1): 6791, 2021 11 23.
Article
in English
| MEDLINE | ID: covidwho-1532053
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, 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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Virus Internalization
/
Lung Injury
/
Angiotensin-Converting Enzyme 2
/
SARS-CoV-2
/
COVID-19
/
COVID-19 Drug Treatment
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
English
Journal:
Nat Commun
Journal subject:
Biology
/
Science
Year:
2021
Document Type:
Article
Affiliation country:
S41467-021-27097-8
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