Suppression of SARS-CoV-2-induced lung injury by ACE2-like carboxypeptidase B38-CAP in COVID-19 mouse model

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 decoy. the carboxypeptidase to degrade angiotensin II (Ang II) 1-7 improves pathologies cardiovascular disease acute lung injury. To address whether enzymatic activity protective against COVID-19, we investigated effects B38-CAP, an ACE2-like enzyme, on SARS-CoV-2-induced Expression was significantly downregulated in lungs SARS-CoV-2-infected hamsters. Recombinant S1 domain or receptor-binding (RBD) Spike also directly expression elevated Ang levels considerably worsened acid-induced injury Treatment with B38-CAP RBD-induced high levels, severe inflammation pulmonary edema through its activity. Consistently, cytokine mRNA impaired functions were improved by treatment. Moreover, humanized transgenic mice, injury, alleviated storms viral RNA levels. These results provide first experimental vivo evidence that increasing potential powerful therapeutic strategy COVID-19.