l entry. Nevertheless, ADAM17/TACE-mediated ACE2 shedding or ACE2 enzymatic activity have been shown to intriguingly correlate positively with viral infection and disease complications [17,19,20]. In contrast, HNL63-CoV, which similarly binds to ACE2 through its spike protein, infects ACE2-bearing cells and mainly induces the common cold, leading to neither ACE2 shedding nor SARS [17]. Moreover, catalytically inactive forms of sACE2 can potently inhibit SARS-CoV infection [19,21], suggesting that events downstream of ACE2 shedding