Fig. 4. Multimeric and biparatopic Bicycles inhibit SARS-CoV-2 VoC.

a Structure of E2 Bicycle in complex with ACE2 showing location of two key VoC mutations L452R (in Delta) and E484K (in Beta). b Infection of 293 T TMPRSS2/ACE2 cells with S-pV displaying the Spike protein from Delta or Beta VoCs, or point mutations L452R (Delta 452) or E484K (Beta 484), in the presence of E2 trimer. Data is the result of three independent experiments presented as mean values +/- SEM. Dose response curves were fitted to obtain IC₅₀ values: Delta = 5700 nM, Delta 452 = 1.4 nM, Beta = 19000 nM, Beta 484 = 4.2 nM. c–f Infection of 293 T TMPRSS2/ACE2 cells with S-pV displaying the Spike protein from VoCs. Data is the result of three independent experiments presented as mean values +/- SEM. Dose response curves were fitted to obtain IC₅₀ values for Alpha (c): E3E5 = 2.1 nM, E4E5 = 0.67 nM, E2c Trimer = 2.5 nM, E2E4 = 1.6 nM. For Beta (d): E3E5 = 400 nM, E4E5 = 25 nM, E2c Trimer = 250 nM, E2E4 = 74 nM. For Delta (e): E3E5 = 61 nM, E4E5 = 2500 nM, E2c Trimer = 73 nM, E2E4 = 1200 nM. For Omicron (f): E1E4 = 44 nM. G Dose response curves for the inhibition of GFP + multinucleated syncytia formation by cells expressing Delta Spike by an epitope group 2 Bicycle E2c or E3E5 biparatopic Bicycle, fit to obtain IC₅₀ values of: E2c trimer = 1.6 µM and E3E5 = 4.5 µM. Data shown is from two independent experiments presented as mean values. Source data are provided as a Source Data file.