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Biochem. Biophys. Res. Commun. · Jan 2021
Identification of antiviral antihistamines for COVID-19 repurposing.
- Leah R Reznikov, Michael H Norris, Rohit Vashisht, Andrew P Bluhm, Danmeng Li, Yan-Shin J Liao, Ashley Brown, Atul J Butte, and David A Ostrov.
- Department of Physiological Sciences, University of Florida College of Veterinary Medicine, Gainesville, FL, USA.
- Biochem. Biophys. Res. Commun. 2021 Jan 29; 538: 173-179.
AbstractThere 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.Copyright © 2020 Elsevier Inc. All rights reserved.
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