Fig. 4: Conformation transitions of Omicron S–FD01 in all states.

The representative bispecific antibody GW01-16L9 (FD01) IgG in complex with the Omicron S trimer. One 16L9 binds to the “up” RBD-1 in the apo S trimer (State 0) to form the State 1 complex. Then, the 22-aa GS linker between 16L9 and GW01 guides GW01 to bind to RBD-1 and push it more open to accommodate GW01, which unlocks the “down” RBD-2 and induces it to the “up” state (State 2). Thus, another 16L9 could easily catch the “up” state RBD-2. The same triggering process then occurs on RBD-2 (State 3 and State 4) and RBD-3 (State 5), allowing the binding of the second and third FD01 to RBD-2 and RBD-3, respectively. Thus, 16L9 scFv and GW01 scFv synergistically induced the RBD-down conformation into 3 RBD-up conformation. Finally, three pairs of Fc regions from FD01s cross-link two trimers and form a trimer dimer (State 6). Black dotted circles show the states of three RBDs in a spike trimer: red triangles represent "up" state, black triangles represent "down" state and the orange one represents "half-up" state. The direction and distance of movement of RBDs from one state to next state is marked.