Figure 1.

Hypothetical model of host cell membrane binding by Omicron subvariant spikes. A network of spike states based on Omicron subvariant structures is shown. Those states populated insufficiently to be seen by cryo-EM are whited out. The unbound RBD modules flicker between up and down states (tall and short blue rectangles, respectively) to yield open state 1.1. Additionally, drawn are the NTDs (blue triangles) and C-terminal remainder of the S subunits (blue line) that span the viral membrane (light grey bar). The host cell membrane (red) is engaged in states 2 and above of the spike trimer structure, which are predicted to prefer binding to concave membranes. The membrane-tethered spike trimer can bind a single ACE-2 receptor (green circle) on the host cell surface in state 3, a second ACE-2 molecule in state 4, and a third ACE-2 molecule to form prefusion state 5. This leads to proposed state 6, where ACE-2-spike complexes stabilize the membrane contact site while a cleaved spike trimer inserts into the host cell surface, drawing it close to the viral membrane to merge lipid bilayers [44]. Adapted from [11].