Identification of antiviral antihistamines for COVID-19 repurposing

Autor: Michael H. Norris, Leah R. Reznikov, Danmeng Li, David A. Ostrov, Yan-Shin J. Liao, Atul J. Butte, Rohit Vashisht, Ashley N. Brown, Andrew P. Bluhm
Rok vydání: 2021
Předmět:
0301 basic medicine
medicine.medical_treatment
sigma
Sigma-1 receptor
Medical Biochemistry and Metabolomics
Pharmacology
Ligands
Biochemistry
Docking
0302 clinical medicine
Catalytic Domain
Receptors
Chlorocebus aethiops
Medicine
Repurposing
Hydroxyzine
education.field_of_study
Diphenhydramine
Angiotensin converting Enzyme-2
Drug repositioning
Infectious Diseases
5.1 Pharmaceuticals
030220 oncology & carcinogenesis
Receptors
Histamine
Antihistamine
Angiotensin-Converting Enzyme 2
Development of treatments and therapeutic interventions
Histamine
Protein Binding
medicine.drug
Biochemistry & Molecular Biology
Population
Histamine Antagonists
Biophysics
Antiviral Agents
Article
Vaccine Related
Medicinal and Biomolecular Chemistry
03 medical and health sciences
Clinical Research
Biodefense
Adjuvant therapy
Animals
Humans
Receptors
sigma
education
Vero Cells
Molecular Biology
SARS-CoV-2
business.industry
Prevention
Drug Repositioning
COVID-19
Cell Biology
Azelastine
COVID-19 Drug Treatment
Emerging Infectious Diseases
Good Health and Well Being
HEK293 Cells
030104 developmental biology
Biochemistry and Cell Biology
business
Zdroj: Biochemical and Biophysical Research Communications
ISSN: 0006-291X
Popis: 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 invitro 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 invitro. 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.
Databáze: OpenAIRE
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