Fig. 4: Ty1 binds to the RBD in ‘up’ and ‘down’ conformation and prevents ACE2 engagement.

a Cryo-EM reconstruction to an overall resolution of 2.9 Å (0.143 FSC) of the spike trimer with three bound molecules of Ty1. b Atomic model (cartoon representation) of trimeric spike in complex with three molecules of Ty1. Three chains of spike are shown in three different colors. The RBD of chain A (light green) is present in ‘up’ conformation while the other two RBDs are captured in ‘down’ conformation. The ACE2 interaction surface of RBD1 and the Ty1 interaction surface is highlighted. Magnified view of RBD2 (in ‘down’ conformation) and Ty1 interaction is shown. CDR1, 2, and 3 of Ty1 are shown in blue, green, and red, respectively. c Ty1 shows a two-pronged inhibition of ACE2 receptor binding through binding the RBD in the ‘up’ conformation and by binding to the neighboring RBD in the ‘down’ conformation. Binding of Ty1 to RBDs (both ‘up’ and ‘down’) would make ACE2 interaction surface inaccessible for ACE2.