Fig. 3

Characterization of the ciclopirox binding sites on HBV core protein. a Overall architecture of the hexamer in the asymmetric unit. The six protomers are colored light orange, orange, light blue, blue, pink, and red. The secondary structure of the protein was calculated using STRIDE⁶². Ciclopirox is shown as a space-filling model. The binding sites at the dimer-dimer interfaces that are not bound by ciclopirox are highlighted by dashed green circles. The black triangle indicates the icosahedral threefold axis of the HBV capsid. Top view (left panel) and side view (right panel). b The ciclopirox binding site in chain B. The view is the same as in the right panel of a. The residues involved in ciclopirox binding are in orange. The simulated annealing omit map superimposed on the refined ciclopirox model was contoured at the 2.5σ level. c Schematic depiction of the HBV core protein-ciclopirox interaction. The residues involved in ciclopirox binding are shown. Y118 and ciclopirox are in blue and green, respectively. d Effect of mutation of Y118 to phenylalanine (Y118F) and chemical modifications of ciclopirox on intracellular HBV capsid assembly. e Comparison of the ciclopirox-bound and -free sites of chains (b, c). The two binding sites are aligned and the residues involved in ciclopirox binding are represented as sticks. The leucine at 19 is omitted for clarity. The view is the same as in b. The rotation of F23 is marked by the red arrow. f Movement of the proline-rich loop 6. The ciclopirox-free pocket is shown, and ciclopirox and loop 6 of the ciclopirox-bound protomer are superimposed on it. The movement of loop 6 is shown by the red arrow. This view is rotated by 90 degrees along the vertical axis from (e). The data in d are representative of three independent experiments and are expressed as mean ± SD. The error bars represent the ± SD. N.A., not available. *p < 0.05; **p < 0.01, as determined by unpaired two-tailed Student’s t-tests. Source data are provided as a Source Data file