Fig. 5: Schematic model of ACE2-mediated SARS-CoV-2 fusion process and fusion intermediates.

a Membrane fusion stages between SARS-CoV-2 and ACE2_VLPs, including initial binding (I), extended intermediates (II), partial backfolding intermediates (III), tightly opposing intermediates (IV), dimpling phase (V), hemifusion (VI), fusion pore (VII), full fusion (VIII), and multiple rounds of fusion (IX). The HIV-1 capsid is depicted in light green, and RNPs are shown in yellow. The membrane states in V–VII are depicted in inset. Trypsin cleavage of S2’ triggers the subsequent processes beyond stage III and completes membrane fusion (IV–VIII) (pink arrows), whereas the WS6 S2 antibody blocks the fusion at stage II (purple arrows). b Models of spike fusion intermediates and the states they are associated with in the schematic above. WS6 antibody binds to spikes in states I and II, inhibiting the refolding of state II intermediate. S2’ cleavage triggers a complete refolding from the state III partial backfolding intermediate and the formation of postfusion spike. The image was generated using PDBs 7a97, 6xr8, 8fdw, 6m1d, and 7TCQ. The fusion peptide is shown in yellow, the transmembrane region in navy, heptad region 1 in light green, heptad region 2 in coral, S2’ cleavage site marked with a dashed red bubble, and WS6 in purple.