Mechanistically, the SARS-CoV-2 RBD protein directly binds and downregulates ACE2 and consequently elevates AngI and AngII, further increasing the NOX1/2 and their mediated inflammation and oxidative stress through AT1R. rACE2 reversed SARS-CoV-2 RBD protein-aggravated LPS-induced ALI by either directly binding SARS-CoV-2 RBD protein or lowering AngI and/or AngII. This evidence concerns the gene ACE2 and acute respiratory distress syndrome.