Fig. 5: Mutations on CDR3 boost the efficacy of VHH77. | Nature Communications

Fig. 5: Mutations on CDR3 boost the efficacy of VHH77.

From: The crystal structure of coronavirus RBD-TMPRSS2 complex provides basis for the discovery of therapeutic antibodies

Fig. 5

a Binding affinities (KD) and half-maximal inhibitory concentrations (IC50) of VHH77 variants for TMPRSS2 catalytic activity. b BLI-based competition analysis of VHH77 variants with HCoV-HKU1 RBD to TMPRSS2. c, d Vero E6-TMPRSS2 cells were pretreated with different concentrations of VHH77-10-Fc (c) or VHH77-11-Fc (d) antibodies for 1 h and then infected with wild-type SARS-CoV-2 or its delta variant (MOI = 0.01). The CPE rates were determined with a Celigo image cytometer at 72 h post-infection. The data points represent the means ± SDs from biological triplicates (n = 3). e Effects of VHH77-Fc, VHH77-10-Fc, and VHH77-11-Fc antibodies on HCoV-HKU1-mediated cell‒cell fusion. The data points represent the means ± SDs from biological triplicates (n = 3). f–h Structural comparisons highlight the differences between the VHH77-10:TMPRSS2 and VHH77:TMPRSS2 interactions. The structures of the VHH77-10:TMPRSS2 and VHH77:TMPRSS2 complexes were overlaid, with CDR3 of VHH77-10 colored orange and CDR3 of VHH77 colored wheat. The remainder of VHH77-10 is shown in gray, and the remainder of VHH77 is in white. TMPRSS2 in the VHH77-10:TMPRSS2 complex is colored mint, while TMPRSS2 in the VHH77:TMPRSS2 complex is colored light mint. Hydrogen bonds and ionic interactions in the VHH77-10:TMPRSS2 complex are represented by black dashed lines. In panel (g), the structure of the HCoV-HKU1 RBD in the RBD:TMPRSS2 complex is overlaid, with the RBM colored salmon.

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