Validation of BKV large T-antigen ATP-binding site as a target for drug discovery.
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.
Zeng
Gang
G
Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
Bueno
Marta
M
Camachos
Carlos J
CJ
Ramaswami
Bala
B
Luo
Chunqing
C
Randhawa
Parmjeet
P
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
D000957:Antigens, Viral, Tumor; D000998:Antiviral Agents; D014764:Viral Proteins; D004265:DNA Helicases