{"doi":"10.17615/cph0-4s39","title":"Identification and Utilization of a Chemical Probe to Interrogate the Roles of PIKfyve in the Lifecycle of β-Coronaviruses","abstract":"From a designed library of indolyl pyrimidinamines, we identified a highly potent and cell-active chemical probe (17) that inhibits phosphatidylinositol-3-phosphate 5-kinase (PIKfyve). Comprehensive evaluation of inhibitor selectivity confirmed that this PIKfyve probe demonstrates excellent kinome-wide selectivity. A structurally related indolyl pyrimidinamine (30) was characterized as a negative control that lacks PIKfyve inhibitory activity and exhibits exquisite selectivity when profiled broadly. Chemical probe 17 disrupts multiple phases of the lifecycle of β-coronaviruses: viral replication and viral entry. The diverse antiviral roles of PIKfyve have not been previously probed comprehensively in a single study or using the same compound set. Our scaffold is a distinct chemotype that lacks the canonical morpholine hinge-binder of classical lipid kinase inhibitors and has a non-overlapping kinase off-target profile with known PIKfyve inhibitors. Our chemical probe set can be used by the community to further characterize the role of PIKfyve in virology.","journal":"UNC Libraries","year":2022,"id":312235,"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":0.9598,"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":333823,"name":"Sharon Taft-Benz","orcid":"0000-0002-0965-8760","position":1,"is_corresponding":false},{"id":392102,"name":"Nathaniel J. Moorman","orcid":"0000-0003-4952-6858","position":2,"is_corresponding":false},{"id":729703,"name":"Peter S. McPherson","orcid":"0000-0001-7806-5662","position":3,"is_corresponding":false},{"id":376426,"name":"Alison D. Axtman","orcid":"0000-0003-4779-9932","position":4,"is_corresponding":false},{"id":273790,"name":"David H. Drewry","orcid":"0000-0001-5973-5798","position":5,"is_corresponding":false},{"id":275061,"name":"Mark T. Heise","orcid":"0000-0001-5829-8477","position":6,"is_corresponding":false},{"id":1009680,"name":"Sophia M. Min","orcid":"0000-0001-9840-2996","position":7,"is_corresponding":false},{"id":671742,"name":"Frances Potjewyd","orcid":null,"position":8,"is_corresponding":false},{"id":891302,"name":"Jeffery L. Smith","orcid":"0000-0003-2189-0420","position":9,"is_corresponding":false},{"id":891301,"name":"Armin Bayati","orcid":"0000-0002-5960-0479","position":10,"is_corresponding":false},{"id":1009681,"name":"Stefanie Howell","orcid":"0000-0002-2039-9245","position":11,"is_corresponding":false},{"id":891300,"name":"Rebekah J. Dickmander","orcid":"0000-0002-5367-6587","position":12,"is_corresponding":false},{"id":1009679,"name":"M. Anwar Hossain","orcid":"0000-0001-9777-0332","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:33:36.072096Z","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":[]}