Structure-activity relationship for the binding of licorice triterpenoids with the spike RBD. (A) SPR analysis of GA and A3 binding to the RBD, respectively. The affinity constant KD values of GA and A3 with RBD were calculated by kinetics analysis. (B) Molecular docking of GA, GA-g, GA-gg, and A3 with RBD (PDB ID: 6M0J), showing the hydrogen bonds (magenta dashes). (C) Inhibitory activities of GA, GA-g, GA-gg and A3 (10 µM) against RBD and the Y453F mutant determined by ELISA, n ≥ 3. RBD and RBD-Y453F (0.5 µg/mL), ACE2 (0.5 µg/mL) were used.