Schematic diagram of the renin-angiotensin system in acute lung failure and proposed SARS-CoV action. The renin-angiotensin system has a crucial role in severe acute lung injury and the SARS-CoV receptor ACE2 has a protective role in acute lung failure. Because ACE2 is a crucial SARS-CoV receptor, SARS-CoV Spike protein binding to ACE2 downmodulates ACE2 expression, and loss of ACE2 expression results in severe acute respiratory failure. The AT1R is the crucial receptor that mediates AngII-induced vascular permeability and severe acute lung injury. SARS-CoV Spike–mediated lung failure can be rescued by inhibition of AT1R. This research was done in in vivo mice cells.