{"doi":"10.17615/q26w-mv98","title":"High-throughput screening identifies a bisphenol inhibitor of SV40 large T antigen ATPase activity","abstract":"The authors conducted a high-throughput screening campaign for inhibitors of SV40 large T antigen ATPase activity to identify candidate antivirals that target the replication of polyomaviruses. The primary assay was adapted to 1536-well microplates and used to screen the National Institutes of Health Molecular Libraries Probe Centers Network library of 306 015 compounds. The primary screen had an Z value of ∼0.68, signal/background = 3, and a high (5%) DMSO tolerance. Two counterscreens and two secondary assays were used to prioritize hits by EC50, cytotoxicity, target specificity, and off-target effects. Hits that inhibited ATPase activity by >44% in the primary screen were tested in dose-response efficacy and eukaryotic cytotoxicity assays. After evaluation of hit cytotoxicity, drug likeness, promiscuity, and target specificity, three compounds were chosen for chemical optimization. Chemical optimization identified a class of bisphenols as the most effective biochemical inhibitors. Bisphenol A inhibited SV40 large T antigen ATPase activity with an IC50 of 41 μM in the primary assay and 6.2 μM in a cytoprotection assay. This compound class is suitable as probes for biochemical investigation of large T antigen ATPase activity, but because of their cytotoxicity, further optimization is necessary for their use in studying polyomavirus replication in vivo.","journal":"UNC Libraries","year":2022,"id":311883,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9248,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1008795,"name":"J.W. Noah","orcid":null,"position":1,"is_corresponding":false},{"id":945832,"name":"J.E. Golden","orcid":null,"position":2,"is_corresponding":false},{"id":1008796,"name":"M. Nebane-Akah","orcid":null,"position":3,"is_corresponding":false},{"id":1006308,"name":"L. Rasmussen","orcid":null,"position":4,"is_corresponding":false},{"id":1008797,"name":"B.E. Maki","orcid":null,"position":5,"is_corresponding":false},{"id":1008798,"name":"S. Ananthan","orcid":null,"position":6,"is_corresponding":false},{"id":1008799,"name":"D.S. Matharu","orcid":null,"position":7,"is_corresponding":false},{"id":1008800,"name":"M. Sosa","orcid":null,"position":8,"is_corresponding":false},{"id":1008801,"name":"S. McKellip","orcid":null,"position":9,"is_corresponding":false},{"id":945840,"name":"J. Aubé","orcid":null,"position":10,"is_corresponding":false},{"id":1008802,"name":"E.L. White","orcid":null,"position":11,"is_corresponding":false},{"id":1008803,"name":"C.W. Evans","orcid":null,"position":12,"is_corresponding":false},{"id":1008804,"name":"N.A. Tower","orcid":null,"position":13,"is_corresponding":false},{"id":1008805,"name":"J.L. Brodsky","orcid":null,"position":14,"is_corresponding":false},{"id":1008794,"name":"S.P. Seguin","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T00:33:32.327694Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}