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. 2022 Apr 20;23(9):4576. doi: 10.3390/ijms23094576

Figure 2.

Figure 2

SARS-CoV-2 entry pathways. Illustration depicting ways SARS-CoV-2 uses to enter cells. (A) Entry by fusion-the direct fusion of the SARS-CoV-2 envelope with the plasma membrane is mediated by the processing of the spike protein after the interaction with the cellular receptor ACE2. The cleavage sites by specific proteases are shown: furin cleaves spike a multibasic motif in the S1/S2 site (priming step), and TMPRSS2 cleaves spike in the S2′ site (activation step). Cleavage by furin seems to occur during the cell exit of SARS-CoV-2 virions. When cells express TMPRSS2, hidden hydrophobic residues of the S2 region are exposed, and SARS-CoV-2 fuse directly with the plasma membrane. (B) Entry by endocytosis-In TMPRSS2-low expressing cells, virus entry occurs by endocytosis. In this case, when the virus reaches the endosomes, it encounters cathepsins (non-specific low pH activated proteases) that activate both SARS-CoV and SARS-CoV-2 spike proteins. Please refer to the main text for a more detailed description of these processes. Image created using BioRender.