CryoEM was used to visualize the effect of the peptides on DENV-2 virions. The surface of virions appeared to change from smooth to rough after incubation with the antiviral peptides. This suggests that there may be an alteration of the arrangement of the surface envelope protein (Figure 4) . Biolayer interferometry was used to measure the kinetics of binding between the peptides and Design of Entry Inhibitor Peptides www.plosntds.org soluble, truncated E protein ( Figure 5 ). These binding studies showed a direct interaction between the peptides and DENV-2 E protein with affinities in the 1 mM range and relatively fast on/off rates. The cryoEM images demonstrate that these inhibitory peptides probably cause structural deformations in intact viral particles, but do not provide information about the kinetics of these changes. It is possible that the peptides trap the viral E proteins in some conformation that is part of the normal breathing of the viral particles, and that this interferes with cell binding and entry.