B9-scFv binding to the cryptic epitope interferes with a stabilizing glycan interaction.A, molecular surface map of the full-length SARS-CoV spike (PDB: 5X5B), colored in magenta, was generated using UCSF Chimera. The yellow surface indicates the proposed epitope of B9-scFv; this region is relatively occluded in all contexts. In an RBD-down conformation, this epitope is pressed against the N-terminal domain of the neighboring protomer, while in the RBD-up conformation it is likely to be inaccessible without extensive clashes. B, ribbon diagram showing the epitope for B9-scFv in yellow on Spike protomer A (magenta). This lies adjacent to the NTD from protomer B (blue) where a glycan on N165 potentially occludes conserved epitope. PDB file: 6VXX. C, Estimation of the half-maximal binding of B9-scFv to cell surface SARS-CoV Spike (n = 2). NTD, N-terminal domain; PDB, Protein Data Bank; RBD, receptor-binding domain.