Figure 1.

SARS-CoV-2 entry is dependent on proteolytic cleavage of the spike glycoprotein mediated through early or late entry pathways.

(a) Schematic diagram of spike glycoprotein highlighting S1/S2 and S2′ cleavage sites. Uniport SARS-CoV-2 spike annotations were used and schematic was generated in Biorender. (b) Structure of spike glycoprotein depicting cleavage locations and select mutants. SARS-CoV-2 structure generated using SWISS-MODEL to depict the S1/S2 cleavage sites and annotated using Pymol. S1/S2 region is depicted in green and S2′ region is in red. Spheres depict the location of select mutations discussed in the text: G614, Q677, and P681. (c) Proteolytic activation of SARS-CoV-2 spike mediates early and late entry pathways. Pathways 1 and 2 show early entry at the cell surface facilitated by exogenous or cell surface proteases, respectively. Pathway 3 shows late entry facilitated by endosomal proteases such as cathepsin L. Model generated using Biorender and adapted from Oguntuyo and Stevens et al.