Figure 3. Molecular basis of broad PD41 mAb-mediated neutralization of PDCoV S variants.

A, Surface renderings of the PDCoV S_SD2018 trimer (gold, cyan and pink) without and with one, two and three bound PD41 Fabs (green and orange for heavy and light chains, respectively) observed by cryoEM. N-linked glycans are rendered as blue spheres. B, Ribbon diagram of the PD41 Fab-bound PDCoV RBD_SD2018 cryoEM structure at 3.0Å resolution obtained through local refinement of the one PD41-Fab bound S structure. PD41 V_{H and} V_L are respectively rendered in green and orange whereas the PDCoV RBD is colored cyan. The PDCoV receptor-binding loops are annotated 1–3 and the PD41 complementary determining regions (CDR) for light and heavy chains are annotated CDR-L1, 2, 3 and CHR-H1, 2, 3. C-D, Zoomed-in views of the interface between PDCoV RBD_SD2018 loop 1 (C) or loops 2 and 3 (D) and the PD41 Fab. Selected hydrogen bonds and salt bridges are shown as black dashed lines. A few side chains are shown in surface representation to highlight shape complementarity. E, PD41 epitope conservation across the panel of PDCoV S variants analyzed. Yellow indicates strict residue conservation whereas orange shows the positions of the M348L and T350R substitutions present in S_{Thailand/S5011/2015}. F, Superimposition of the PD41-bound PDCoV RBD structure with the PDCoV S ectodomain trimer structure (PDB 6BFU)³⁵ showing that PD41 could not bind to a closed S trimer without structural changes due to masking of the receptor-binding loops and resulting steric clashes (red star).