title: Validation of BKV large T-antigen ATP-binding site as a target for drug discovery.
abstract: BK virus large T antigen (LTA) is a hexameric protein with a helicase activity that is powered by ATP hydrolysis. A mutant virus with Lys420Ala, Arg421Ala, and Asp504Ala mutations at the ATP binding sites showed marked reduction in viral fitness. This observation indicates that high throughput screening for ATPase inhibitors will be valid strategy to discover anti-BKV drugs. Pilot screening of 300 compounds from the Tim Tec ActiTarg K library identified a compound, STO18584, with selectivity index of 19.2.
authors.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Zeng
authors.forename: Marta
authors.initials: M
authors.lastname: Bueno
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Camachos
authors.forename: Bala
authors.initials: B
authors.lastname: Ramaswami
authors.forename: Chunqing
authors.initials: C
authors.lastname: Luo
authors.forename: Parmjeet
authors.initials: P
authors.lastname: Randhawa
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D000957:Antigens, Viral, Tumor / Q000235:genetics / Q000378:metabolism*; D000998:Antiviral Agents / Q000494:pharmacology; D001739:BK Virus / Q000187:drug effects*; D001665:Binding Sites; D004265:DNA Helicases / Q000037:antagonists & inhibitors* / Q000235:genetics; D004353:Drug Evaluation, Preclinical; D020125:Mutation, Missense; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D000957:Antigens, Viral, Tumor; D000998:Antiviral Agents; D014764:Viral Proteins; D004265:DNA Helicases