A coronavirus contains four structural proteins, namely spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins. These proteins assemble around a lipid bilayer to provide the shell enclosing the viral genome (Figure 4A; Tang et al., 2020). Homotrimers of S protrude from the viral surface, and are densely decorated by N-linked glycans, creating the “crown” (“Corona” in Latin) that christens this virus group (Walls et al., 2016). S is a ∼180 kDa glycoprotein anchored in the viral membrane, which plays the most important roles in viral attachment, fusion and entry (Ou et al., 2020). Sequence analysis has shown that SARS-CoV-2 S protein shares 76% of the primary sequence with the corresponding S of human SARS-CoV (Ou et al., 2020). Accordingly, it has been early proposed that SARS-CoV-2 utilizes a similar cell entry mechanism as SARS-CoV, pivoted on S protein. This hypothesis has been confirmed from an experimental point of view. By using pseudotyped virus bearing SARS-CoV S or SARS-CoV-2 S, it was shown that a large panel of cell lines allows comparable entry of SARS-CoV or SARS-CoV-2 viruses (Hoffmann et al., 2020b; Walls et al., 2020).