ACE2-like carboxypeptidase B38-CAP protects from SARS-CoV-2-induced lung injury. Academic Article uri icon

Overview

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.

publication date

  • November 23, 2021

Research

keywords

  • Angiotensin-Converting Enzyme 2
  • COVID-19
  • COVID-19 Drug Treatment
  • Lung Injury
  • SARS-CoV-2
  • Virus Internalization

Identity

PubMed Central ID

  • PMC8610983

Scopus Document Identifier

  • 85119866320

Digital Object Identifier (DOI)

  • 10.1093/cid/ciaa325

PubMed ID

  • 34815389

Additional Document Info

volume

  • 12

issue

  • 1