Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. Binding to human ACE2 receptor and internalization of the virus into the endosomes of the host cell induces conformational changes in the Spike glycoprotein (PubMed:32142651, PubMed:32221306, PubMed:32075877, PubMed:32155444). Binding to host NRP1 and NRP2 via C-terminal polybasic sequence enhances virion entry into host cell (PubMed:33082294, PubMed:33082293). This interaction may explain virus tropism of human olfactory epithelium cells, which express high level of NRP1 and NRP2 but low level of ACE2 (PubMed:33082293). The stalk domain of S contains three hinges, giving the head unexpected orientational freedom (PubMed:32817270). Uses human TMPRSS2 for priming in human lung cells which is an essential step for viral entry (PubMed:32142651). Can be alternatively processed by host furin (PubMed:32362314). Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membrane fusion within endosomes.
