Histamine receptors and COVID-19
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Inflammation Research
REVIEW
Histamine receptors and COVID‑19 Madeleine Ennis1 · Katerina Tiligada2 Received: 29 September 2020 / Revised: 29 October 2020 / Accepted: 4 November 2020 © Springer Nature Switzerland AG 2020
Abstract Objective Reports that the over-the-counter histamine H 2 receptor antagonist famotidine could help treat the novel coronavirus disease (COVID-19) appeared from April 2020. We, therefore, examined reports on interactions between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and histamine receptor antagonists. Methods A systematic literature search was performed by 19 September 2020, and updated on 28 October 2020, in PubMed, Scopus, Cochrane Library and Google Scholar using (COVID-19 OR coronavirus OR SARS-CoV-2) AND (histamine antagonist OR famotidine OR cimetidine). ClinicalTrials.gov was searched for COVID-19 and (famotidine or histamine). Results Famotidine may be a useful addition in COVID-19 treatment, but the results from prospective randomized trials are as yet awaited. Bioinformatics/drug repurposing studies indicated that, among several medicines, H1 and H2 receptor antagonists may interact with key viral enzymes. However, in vitro studies have to date failed to show a direct inhibition of famotidine on SARS-CoV-2 replication. Conclusions Clinical research into the potential benefits of H 2 receptor antagonists in managing COVID-19 inflammation began from a simple observation and now is being tested in multi-centre clinical trials. The positive effects of famotidine may be due to H2 receptor-mediated immunomodulatory actions on mast cell histamine–cytokine cross-talk, rather than a direct action on SARS-CoV-2. Keywords COVID-19 · Histamine · Histamine receptor · Mast cells · Immunomodulation · SARS-CoV-2
Introduction The novel coronavirus disease (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) that emerged in the Chinese province of Hubei in December 2019 and rapidly spread worldwide [1]. COVID19 is an ongoing major public health threat declared as pandemic by the World Health Organization (WHO) on 11 March 2020. The clinical manifestations of the disease range from mild to severe non-specific symptoms and signs with Responsible Editor: John Di Battista. * Katerina Tiligada [email protected] 1
The Wellcome‑Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queens University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK
Department of Pharmacology, Medical School, National and Kapodistrian University of Athens, M. Asias 75, 11527 Athens, Greece
2
pneumonia and acute respiratory distress syndrome (ARDS) being common, frequently fatal, complications [2]. At present, there are no vaccines against SARS-CoV-2. Moreover, more than 20 therapeutic agents, mostly repurposed drug candidates, including the histamine H 2 receptor antagonist famotidine, are being evaluated in numerous clinical trials for the treatment of COVID-19 [3].
SARS‑CoV‑2 The SARS-CoV-2
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