Angiotensin-converting enzyme (ACE) 2 is a multi-functional protein, including carboxypeptidase, virus receptor and regulator of amino acid transporter. ACE2 is an essential receptor for cell entry of SARS-CoV-2, resulting in explosive increase of infected people and COVID-19 patients. On the other hand, ACE2 is a carboxypeptidase which degrades angiotensin II, and thereby is a critical regulator of cardiovascular physiology and pathology. The enzymatic activity of ACE2 is protective against acute respiratory distress syndrome (ARDS). Upon infection, both SARS-CoV-2 and SARS coronaviruses downregulates ACE2 expression, likely associated with the pathogenesis of ARDS. Soluble forms of recombinant ACE2 can be utilized as a decoy to neutralize SARS-CoV-2 and a supplementation of ACE2 carboxypeptidase activity, whereas the cost for mass-production of recombinant ACE2 in mammalian cells is high and thus being obstacle for clinical development. We have identified B38-CAP as a bacteria-derived ACE2-like enzyme, which degrades angiotensin II in mice and is easily prepared in E. coli protein expression system (Nat Commun. 2020). Importantly, B38-CAP protects from SARS-CoV-2 infection-induced lung injury in mice and hamsters (Nat Commun. 2021). Our results indicate that increasing ACE2-like enzymatic activity is a potential therapeutic strategy to alleviate lung pathologies in COVID-19 patients and also implicate the utility of bacteria-derived generic recombinant protein in drug development.