Figure 5

Interaction pharmacophore for the Palm I subdomain. Overlay of PDB coordinates of the three major chemical classes of NS5B palm I inhibitors A) class I (Benzothiazoles), B) class II (Benzo thiadiazines), C) class III (Benzodiazepines)). D) Overlaid complexes at the thumb II site (green dotted lines show polar interactions, different coordinates are colored differently, partial receptor surface is colored according to the interpolated charge-showing the whitish neutral regions)(polar hydrogens displayed in section C) all classes for Palm I shown in A, B, and C fill the deep hydrophobic pocket and shared TYR448 as a backbone HB acceptor. A) ASP318 also had polar interactions at the backbone. SER556 and ASN291 had hydrogen bond (HB) interactions through the terminal hydroxyl and amide groups with all members of class I.B) ASP318, GLY449 and ASN 291 were also involved in the same manner in addition to the terminal polar groups of SER 556 and CYS 366.C) shows that replacing the ketone on the hexene ring by a sulphone group expands the hydrogen bonding from TYR448 to TYR448 and GLY449, additionally, SER 367 HB seemed a common feature and to a lesser extent SER368. D) The main residues forming common polar interactions were SER476, TYR477 -as backbone HB acceptors and ARG 501 through the guanidinium group. A well defined π stacking was noticed between the histidine's imidazole ring and the filibuvir's (3FRZ ligand) triazolo pyrimidine group.