Figure 5. Glycans promote host capture.

(A) Snapshot of the glycosylated Spike protein with the head domain in a caged configuration (glycans not shown). Caging allows the fusion peptide tails to extend toward and engage the host membrane. $d_{\mathrm{FP}}$ is the distance of the center of mass of each fusion peptide from the viral membrane surface. To calculate the probability of host capture, different values of the virion-host distance (d_host) were considered. (B) Representative simulated trajectory, showing $d_{\mathrm{FP}}$ for each of the fusion peptides in a single S2 subunit. For reference, a d_host value of 30 nm is indicated by a dashed line. (C) The probability of membrane fusion is expected to be proportional to the probability that at least one tail extends to the host membrane ($d_{\mathrm{FP}}>d_{\mathrm{host}}$). There is a higher probability of extending to larger d_host values when glycans are present (black vs. red curves). This is due to the glycan-induced delay of head rotation (Figure 2), which ensures the HR1 helix remains directed towards the host as the FPs sample extended configurations. (D–F) The probability that 1, 2, or 3 FPs exceed d_host. In all cases, the presence of glycans shifts the distribution to larger values of d_host, indicating an increased probability of capturing the host. This reveals a critical role for glycans during cell invasion.