Next, the researchers tested this group of antihistamines for their ability to inhibit the coronavirus in a combination of human and primate cells. Three of the drugs—hydroxyzine, diphenhydramine and azelastine—showed direct, statistically significant antiviral effects on the SARS-CoV-2 virus.
Hydroxyzine, sold as Atarax, and the nasal spray azelastine are prescription medications while diphenhydramine is sold over-the-counter as Benadryl, a treatment for cold and allergy symptoms.
The drugs were tested at different concentrations to measure how much is required to inhibit the virus.
While the findings are encouraging, Ostrov cautions against self-medicating with antihistamines as a COVID-19 prevention or treatment. So-called "off-label" use of medications should only take place after a detailed consultation with a physician, he said.
Among the three medications, azelastine was found to inhibit the SARS-CoV-2 virus at a dose that was smaller than the amount prescribed as a nasal spray. The other two antihistamines required higher drug concentrations than currently recommended dosing levels to achieve antiviral activity in cells. That doesn't make diphenhydramine any less of a potential COVID-19 therapy for now, especially considering its ubiquity and over-the-counter status, Ostrov said. Clinical trials will be necessary to establish the drugs' effectiveness in prevention, early treatment and as a secondary therapy for severe COVID-19.
Reznikov said the data suggest these three antihistamines may work by either disrupting the virus's interactions with ACE2 or by binding with another protein that may interfere with viral replication. The protein, known as a sigma receptor, is part of a cell's communications network.
