English: Crystal structure of the PEDV 3CLpro in complex with GC376. (A) Electron density map of GC376 (2Fo-Fc, contoured at 1.0 σ). The bisulfite group of GC376 was removed, and the compound formed a covalent bond with Cys144; (B) three-dimensional structure of the substrate-binding pockets occupied by GC376. The pocket is shown as the surface, and the two residues Thr 47 and Asn 141 are shown as sticks. The distance between the two residues is labeled. GC376 is shown in yellow as sticks. The glutamine surrogate ring and the leucine of GC376 fit comfortably into the S1 and S2 binding sites, respectively. The 6-membered aromatic ring of GC376 points to the solvent; (C) diagram of the detailed molecular interactions between GC376 and the protease. The residues of the pockets are represented in green as lines, and GC376 is shown in yellow as sticks. Hydrogen bond interactions are shown as black dashed lines; (D) structural diagram of the distributions of hydrophobic and hydrophilic interactions at the interface of the PEDV 3CLpro in complex with GC376. The residues of the protease are shown as orange sticks and red arcs with spokes. GC376 is shown in blue as sticks. Carbon, nitrogen, oxygen and sulfur atoms are shown as black, blue, red and yellow circles, respectively. Hydrogen bonds are shown as green dashed lines labeled with the distance between the donor atom and corresponding acceptor atom. Hydrophobic interactions are demonstrated by arcs with spokes radiating toward the atoms (with spokes around) or residues (shown as arcs with spokes) they contact.