Once the SP is bound to ACE2, the SP is subject to proteolytic cleavage into S1 and S2.20One of the most well-known proteolytic enzymes that performs SP cleavage is transmembrane protease, serine 2 (TMPRSS2).22, 23, 24TMPRSS2 colocalizes with ACE2 on multiple cell types, including type II pneumocytes and cardiac myocytes and is thought to play a key role in the infection of the pulmonary and cardiovascular system.8, 25, 26, 27, 28, 29Once cleaved, S1 is released (along with ACE2) and S2 remains attached to the host cell, playing a role in cell–virus cellular membrane fusion. Here, ACE2 is linked to infection.