A Spike-destructing human antibody effectively neutralizes Omicron-included SARS-CoV-2 variants with therapeutic efficacy
Fig 4
Ab08 neutralizes SARS-CoV-2 by destructing S trimer.
(A-B) Structural alignment of Ab08 to the S trimer structure (PDB ID 7WLY) reveals severe clashes with the N-terminal domain (NTD) in cases of both the “down”-RBD (A) and the “up”-RBD conformation (B). The epitope of Ab08 is colored green. The three protomers of S and the RBD of the protomer A are color-coded as indicated in (i). In (ii), the RBD from protomer A is shown as surface representation, and Ab08 (magenta) and the NTD from protomer C (orange) are shown as ribbon representations. The two glycans are shown as cyan sticks. In (iii), the disruption of the interactions between NTD N165-linked glycans (Cyan) and RBD by Ab08 is highlighted. (C-E) 2D class averages of Negative-staining particles of S-2P showing typical S trimer features (C) were lost upon incubation with Ab08 (D), but not with an RBM-targeting control mAb (CB6, E) [22]. Raw images are in S7 Fig. In E, the 2D classes show binding of two CB6 molecules per S trimer and CB6 may induce more “up”-RBD population, a phenomenon that has been reported for other RBM-targeting antibodies [44].