Figure 1.

Pathophysiological consequences of ADAM17 over-activation in SARS-CoV-2 infection. After the binding of SARS-S to ACE2, the S-protein undergoes a proteolytic cleavage by TMPRSS2, and the virus enters the host cell. The attachment of the S protein to ACE2 triggers ADAM17 activation, increasing mACE2 downmodulation, reducing surface ACE2 expression. The increased ADAM17-mediated ACE2 shedding exacerbates the imbalance of RAS, in a looping feedback manner and increases inflammation by TNF-α the IL6 cytokine receptor (IL6R) and growth factor amphiregulin (AREG) cleavage. Finally, the sACE2 release by ADAM17 cleavage might block the viral particles entry.