Validation of BKV large T-antigen ATP-binding site as a target for drug discovery

Gang Zeng; Marta Bueno; Carlos J Camachos; Bala Ramaswami; Chunqing Luo; Parmjeet Randhawa

doi:10.1016/j.antiviral.2008.11.004

Validation of BKV large T-antigen ATP-binding site as a target for drug discovery

Antiviral Res. 2009 Feb;81(2):184-7. doi: 10.1016/j.antiviral.2008.11.004. Epub 2008 Dec 11.

Authors

Gang Zeng¹, Marta Bueno, Carlos J Camachos, Bala Ramaswami, Chunqing Luo, Parmjeet Randhawa

Affiliation

¹ Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.

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.

MeSH terms

Amino Acid Substitution / genetics
Antigens, Viral, Tumor / genetics
Antigens, Viral, Tumor / metabolism*
Antiviral Agents / pharmacology
BK Virus / drug effects*
Binding Sites
DNA Helicases / antagonists & inhibitors*
DNA Helicases / genetics
Drug Evaluation, Preclinical
Mutation, Missense
Viral Proteins / antagonists & inhibitors*
Viral Proteins / genetics

Substances

Antigens, Viral, Tumor
Antiviral Agents
Viral Proteins
DNA Helicases

Abstract

MeSH terms

Substances

Grants and funding