During infection, the spike interacts with the cell surface receptor, such as human aminopeptidase N (APN) for HCoV-229E, angiotensin-converting enzyme 2 (ACE2) for HCoV-NL63, SARS-CoV and SARS-CoV-2, and dipeptidyl peptidase 4 (DPP4) for MERS-CoV, via the RBD in the form of the trimer, followed by the cleavage of the spike by host proteases, such as the cell surface serine protease (TMPRSS2), furin, endosomal cathepsins L, and/or lysosomal proteases, at the boundary of the S1/S2 and S2′ site [18]. Here, ACE2 is linked to infection.