{"doi":"10.1101/2021.10.08.463687","title":"Cetylpyridinium chloride (CPC) reduces zebrafish mortality from influenza infection: Super-resolution microscopy reveals CPC interference with multiple protein interactions with phosphatidylinositol 4,5-bisphosphate in immune function","abstract":"Abstract The COVID-19 pandemic raises significance for a potential influenza therapeutic compound, cetylpyridinium chloride (CPC), which has been extensively used in personal care products as a positively-charged quaternary ammonium antibacterial agent. CPC is currently in clinical trials to assess its effects on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) morbidity. Two published studies have provided mouse and human data indicating that CPC may alleviate influenza infection, and here we show that CPC (0.1 μM, 1 hour) reduces zebrafish mortality and viral load following influenza infection. However, CPC mechanisms of action upon viral-host cell interaction are currently unknown. We have utilized super-resolution fluorescence photoactivation localization microscopy to probe the mode of CPC action. Reduction in density of influenza viral protein hemagglutinin (HA) clusters is known to reduce influenza infectivity: here, we show that CPC (at non-cytotoxic doses, 5-10 µM) reduces HA density and number of HA molecules per cluster within the plasma membrane of NIH-3T3 mouse fibroblasts. HA is known to colocalize with the negatively-charged mammalian lipid phosphatidylinositol 4,5-bisphosphate (PIP 2 ); here, we show that nanoscale co-localization of HA with the PIP 2 -binding Pleckstrin homology (PH) reporter in the plasma membrane is diminished by CPC. CPC also dramatically displaces the PIP 2 -binding protein myristoylated alanine-rich C-kinase substrate (MARCKS) from the plasma membrane of rat RBL-2H3 mast cells; this disruption of PIP 2 is correlated with inhibition of mast cell degranulation. Together, these findings offer a PIP 2 -focused mechanism underlying CPC disruption of influenza and suggest potential pharmacological use of this drug as an influenza therapeutic to reduce global deaths from viral disease.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":219441,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9508,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":400765,"name":"Sasha R. Weller","orcid":null,"position":1,"is_corresponding":false},{"id":400760,"name":"Bright Obeng","orcid":null,"position":2,"is_corresponding":false},{"id":818690,"name":"Brandy L. Soos","orcid":null,"position":3,"is_corresponding":false},{"id":399151,"name":"Bailey West","orcid":"0000-0003-1346-9812","position":4,"is_corresponding":false},{"id":399152,"name":"Christian M. Potts","orcid":"0009-0007-7794-7840","position":5,"is_corresponding":false},{"id":400759,"name":"Suraj Sangroula","orcid":null,"position":6,"is_corresponding":false},{"id":400764,"name":"Marissa Kinney","orcid":null,"position":7,"is_corresponding":false},{"id":400763,"name":"John E. Burnell","orcid":null,"position":8,"is_corresponding":false},{"id":413594,"name":"Benjamin L. King","orcid":"0000-0001-6463-1336","position":9,"is_corresponding":false},{"id":399155,"name":"Julie A. Gosse","orcid":"0000-0002-2457-4039","position":10,"is_corresponding":false},{"id":399154,"name":"Samuel T. Hess","orcid":"0000-0003-2359-6540","position":11,"is_corresponding":false},{"id":399150,"name":"Prakash Raut","orcid":"0009-0000-2015-7396","position":0,"is_corresponding":true}],"reference_count":114,"raw_metadata":null,"created_at":"2026-07-18T23:53:38.409982Z","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":[]}