{"doi":"10.1016/j.bbrc.2020.11.095","title":"Identification of antiviral antihistamines for COVID-19 repurposing","abstract":"There is an urgent need to identify therapies that prevent SARS-CoV-2 infection and improve the outcome of COVID-19 patients. Although repurposed drugs with favorable safety profiles could have significant benefit, widely available prevention or treatment options for COVID-19 have yet to be identified. Efforts to identify approved drugs with in vitro activity against SARS-CoV-2 resulted in identification of antiviral sigma-1 receptor ligands, including antihistamines in the histamine-1 receptor binding class. We identified antihistamine candidates for repurposing by mining electronic health records of usage in population of more than 219,000 subjects tested for SARS-CoV-2. Usage of diphenhydramine, hydroxyzine and azelastine was associated with reduced incidence of SARS-CoV-2 positivity in subjects greater than age 61. We found diphenhydramine, hydroxyzine and azelastine to exhibit direct antiviral activity against SARS-CoV-2 in vitro. Although mechanisms by which specific antihistamines exert antiviral effects is not clear, hydroxyzine, and possibly azelastine, bind Angiotensin Converting Enzyme-2 (ACE2) and the sigma-1 receptor as off-targets. Clinical studies are needed to measure the effectiveness of diphenhydramine, hydroxyzine and azelastine for disease prevention, for early intervention, or as adjuvant therapy for severe COVID-19.","journal":"Biochemical and Biophysical Research Communications","year":2021,"id":3078,"datarank":0.6766289259775276,"base_score":4.51085950651685,"endowment":4.51085950651685,"self_citation_contribution":0.6766289259775276,"citation_network_contribution":0.0,"self_endowment_contribution":0.6766289259775276,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":90,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0509,"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":34143,"name":"Michael H. Norris","orcid":"0000-0002-5285-0432","position":1,"is_corresponding":false},{"id":32096,"name":"Rohit Vashisht","orcid":"0000-0002-2938-7259","position":2,"is_corresponding":false},{"id":34144,"name":"Andrew P. Bluhm","orcid":null,"position":3,"is_corresponding":false},{"id":34145,"name":"Danmeng Li","orcid":"0000-0002-6905-554X","position":4,"is_corresponding":false},{"id":34146,"name":"Yan-Shin J. Liao","orcid":null,"position":5,"is_corresponding":false},{"id":34147,"name":"Ashley Brown","orcid":"0000-0002-3167-7087","position":6,"is_corresponding":false},{"id":51,"name":"Atul Janardhan Butte","orcid":"0000-0002-7433-2740","position":7,"is_corresponding":false},{"id":34148,"name":"David A. Ostrov","orcid":"0000-0002-4696-875X","position":8,"is_corresponding":false},{"id":34149,"name":"Yan‐Shin Liao","orcid":null,"position":9,"is_corresponding":false},{"id":34150,"name":"Ashley N. Brown","orcid":"0000-0001-9993-5241","position":10,"is_corresponding":false},{"id":34142,"name":"Leah R. Reznikov","orcid":"0000-0002-4074-9070","position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":null,"created_at":"2026-03-01T18:20:47.508186Z","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":[]}