Fig. 1.

Virtual ligand screening of the NCI compound library against WNV NS3pro. The complete NCI database (∼275,000 compounds) was docked into the NS2B cofactor-binding cavity in the NS3pro domain. The initial screening led to identification of the top 80 hits, which were then re-docked under more stringent conditions and ranked according to their relative binding energy E. The top 50 predicted binders were ordered from NCI and their inhibitory potency was tested in the in vitro cleavage assays. A significant fraction of the tested ligands were true-positives (active, gray dots), whereas other ligands were false-positives (inactive, white dots). WNV, West Nile virus.