{"doi":"10.3389/fphar.2021.633680","title":"COVID-19: Famotidine, Histamine, Mast Cells, and Mechanisms","abstract":"SARS-CoV-2 infection is required for COVID-19, but many signs and symptoms of COVID-19 differ from common acute viral diseases. SARS-CoV-2 infection is necessary but not sufficient for development of clinical COVID-19 disease. Currently, there are no approved pre- or post-exposure prophylactic COVID-19 medical countermeasures. Clinical data suggest that famotidine may mitigate COVID-19 disease, but both mechanism of action and rationale for dose selection remain obscure. We have investigated several plausible hypotheses for famotidine activity including antiviral and host-mediated mechanisms of action. We propose that the principal mechanism of action of famotidine for relieving COVID-19 symptoms involves on-target histamine receptor H 2 activity, and that development of clinical COVID-19 involves dysfunctional mast cell activation and histamine release. Based on these findings and associated hypothesis, new COVID-19 multi-drug treatment strategies based on repurposing well-characterized drugs are being developed and clinically tested, and many of these drugs are available worldwide in inexpensive generic oral forms suitable for both outpatient and inpatient treatment of COVID-19 disease.","journal":"Frontiers in Pharmacology","year":2021,"id":149498,"datarank":0.6995158641168101,"base_score":4.663439094112067,"endowment":4.663439094112067,"self_citation_contribution":0.6995158641168101,"citation_network_contribution":0.0,"self_endowment_contribution":0.6995158641168101,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":105,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"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":637331,"name":"Philip Tisdall","orcid":null,"position":1,"is_corresponding":false},{"id":636089,"name":"Philip Fremont‐Smith","orcid":"0000-0002-2061-5809","position":2,"is_corresponding":false},{"id":103671,"name":"Yongfeng Liu","orcid":"0000-0002-8649-7892","position":3,"is_corresponding":false},{"id":103670,"name":"Xi‐Ping Huang","orcid":"0000-0002-2585-653X","position":4,"is_corresponding":false},{"id":1481,"name":"Kris M. 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