Figure 2 Proposed Mechanism of Entry for SARS-CoV-2 Via ACE2
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to the catalytic site of ACE2 via its S protein. To gain access to the host cytosol, the S protein undergoes acid dependent proteolytic cleavage by ACE2, tumor necrosis factor (TNF)-α, transmembrane protease serine 2 (TMPRRS2), which results in the formation of an S1 and S2 subunit. S2 fusion peptide inserts into the membrane, which allows for clatherin-dependent endocytosis of ACE2-SARS-CoV-2. Viral binding stimulates TNF-α and calmodulin inhibitors to promote ectodomain cleavage of ACE2. ADAM 17 = disintegrin and metalloprotease 17; other abbreviations as in Figure 1.