We started from 4 naïve billion scale libraries with different sizes of disulfide constrained rings (SCX12C, SXCX10CX, SX2CX8CX2, SX3CX9C) and pre-selected each library for 3 rounds using NS3aH1 binding and grazoprevir elution (Figure , Figure ). We considered late-stage re-shaping to be practical at the point of the selection when the diversity decreased from billion scale to a diversity manageable within the sequencing depth of NGS (< 10 6 peptides). We also observed that diversity collapsed < 10 5 peptides the output of Round 3. Therefore, we decided to return to input of Round 3 and performed reshaping of the library to re-run Round 3 of selection.