Figure 6. Schematic of fusion mechanism of the Spike protein.

Initial activation of the Spike protein (left) is associated with release of S1, which is triggered by cleavage at the S2’ site and ACE2 receptor binding. When glycans are present (top), HG will enter a caged ensemble where the FPs search for, and capture, the host membrane. HG can then escape the cage, which draws the viral and host membranes together and leads to fusion. In the absence of glycans (bottom), HG can bypass the caged ensemble, resulting in a failed attempt to recruit the host.