title: High-throughput virtual screening lead to discovery of non-peptidic inhibitors of West Nile virus NS3 protease.
abstract: The non-structural 3 protease is an essential flaviviral enzyme and therefore one of the most promising targets for drug development against West Nile virus infections. In this chapter, we discuss in detail the computational methods used in the previous two docking campaigns which lead to the discovery of non-peptidic low micromolar inhibitors. Not only an X-ray structure but also an alternative conformation generated from molecular dynamic simulations is used in the in silico screening. Moreover, unique scoring schemes are developed based on the properties of the binding site of the protein.
authors.affiliation: Department of Biochemistry, University of Zurich, Zurich, Switzerland. dhuang@bioc.uzh.ch
authors.forename: Danzhi
authors.initials: D
authors.lastname: Huang
mesh_terms: D000998:Antiviral Agents / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology*; D055808:Drug Discovery; D057166:High-Throughput Screening Assays / Q000379:methods*; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000494:pharmacology; D011480:Protease Inhibitors / Q000032:analysis* / Q000737:chemistry / Q000494:pharmacology; D011487:Protein Conformation; D020365:RNA Helicases / Q000037:antagonists & inhibitors; D012697:Serine Endopeptidases; D014584:User-Computer Interface; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D014902:West Nile virus / Q000187:drug effects / Q000201:enzymology*; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D010455:Peptides; D011480:Protease Inhibitors; D020365:RNA Helicases; D012697:Serine Endopeptidases; D017361:Viral Nonstructural Proteins; C060028:NS3 protein, flavivirus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases