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. Endogenous ACE2 is a receptor for SARS-CoV-2 and a recombinant soluble ACE2 protein can inhibit SARS-CoV-2 infection acting as a decoy. Here the authors show that B38-CAP, an ACE2-like enzyme but not a decoy for the virus, is protective against SARS-CoV-2-induced lung injury in animal models.
【저자키워드】 SARS-CoV-2, Respiratory distress syndrome, peptides, 【초록키워드】 Treatment, pathology, ACE2, spike, SARS-COV-2 infection, Infection, lung, cardiovascular disease, Symptom, animal models, Lung injury, virus, angiotensin-converting enzyme 2, acute lung injury, human ACE2, Protein, Lungs, edema, receptor, in vivo, Pathologies, ACE2 expression, therapeutic strategy, COVID-19 patients, Protective, Lung pathology, Angiotensin-converting enzyme, Angiotensin II, soluble ACE2, Evidence, angiotensin, recombinant, decoy, enzymatic activity, enzyme, cell entry, SARS-CoV-2-infected hamsters, Elevation, transgenic mice, lung edema, carboxypeptidase, endogenous, IMPROVE, significantly, inhibit, downregulated, downregulate, alleviate, acting, degrade, inhibit SARS-CoV-2, not neutralize, SARS-CoV-2-infected hamster, 【제목키워드】 PROTECT,