SPR was used to measure (A) association rates and (B) dissociation rates for PLpro inhibitors: GRL0617 (1), ZN-2-184 (5), ZN-3-80 (65), XR8-24 (73), XR8-23 (72), XR8-89 (94). (C) Binding affinity (KD determined by SPR) was used to demonstrate potential cooperativity by engaging multiple weak interactions across multiple binding sites.