For initial entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into cells, the large viral Spike (S) protein needs to be primed by host proteases. For SARS-CoV-2 that is the serine protease TMPRSS2. After binding to its functional receptor, angiotensin-converting enzyme 2 (ACE2), the virus undergoes endocytosis. After endocytosis of the viral complex, surface ACE2 is further down-regulated, resulting in unopposed angiotensin 2 accumulation. Local activation of the angiotensin pathway system may mediate lung injury responses to viral insults.
ACE denotes angiotensin-converting enzyme and ARB angiotensin-receptor blocker.