Fig 1.
A chart for the virtual screen targeting HCV NS5B polymerase.
Table 1.
Results of RF model validation by an independent test set.
Fig 2.
Redocked binding modes of the co-crystalized inhibitors in the active site of NS5B polymerase.
(A-B) the palm I region, (C-D) the thumb I region, (E-F) the thumb II region.
Fig 3.
E-pharmacophore hypotheses with energetically favorable sites from the six crystal structures.
Pink sphere represents hydrogen-bond acceptor (A); orange ring represents aromatic ring (R); blue sphere represents hydrogen-bond donor (D); red sphere represents negatively ionizable (N); green spheres represent hydrophobic (H).
Table 2.
E-pharmacophore features and the scores for each feature in e-pharmacophore hypotheses generated from the six crystal structures.
Table 3.
Validation of the six e-pharmacophore hypotheses.
Table 4.
The RMSD (Å) for glide HTVS, SP and XP.
Table 5.
Number of hits retrieved at the PB-VS and DB-VS stage of screening.
Table 6.
Antiviral activity and cytotoxicity of the 5 hits.
Fig 4.
Structures of the 5 hit compounds.
Fig 5.
The structures of known NS5B inhibitors (K1 –K5).
These inhibitors have the highest Tcs with N1 –N5, respectively.
Fig 6.
The binding poses of compound N1 –N5 in the respective binding pocket of NS5B polymerase.
(A) N1; (B) N2; (C) N3; (D) N4; (E) N5. Potential hydrogen bonding interaction are shown as dashed lines.