Bilastine for COVID-19

With the rollout of multiple COVID-19 vaccines, adjunctive treatments for COVID-19 have received less attention. Breakthrough infections post-vaccination (including boosters) underscore the need to continue evaluating repurposed drugs and nutraceuticals as candidate adjunctive treatments. Early clinical studies of antihistamines hypothesized that targeting mast cells (and/or histamine receptors) might benefit COVID-19 patients. In cultured human coronary artery endothelial cells, histamine potentiated spike-mediated angiotensin-converting enzyme 2 internalization; this effect can be blocked by the antihistamine famotidine. This literature review focuses on clinical studies of antihistamines, mast cell stabilizers, and leukotriene receptor antagonists for COVID-19 patients. Several antihistamines and mast cell-targeting agents, including fluvoxamine, cyproheptadine, hydroxyzine, and antihistamines used alone or with azithromycin (dexchlorpheniramine, cetirizine, loratadine, and ebastine), as well as azelastine, famotidine (standard or high-dose), high-dose famotidine with celecoxib, and the flavonoid mast cell stabilizer quercetin, have been reported to be associated with clinical benefits in COVID-19 patients. Multiple studies have reported mixed results for aspirin, montelukast, and normal-dose famotidine; patients taking aspirin often have associated COVID-19 risk factors. In the context of current standard-of-care treatments, clinical studies evaluating candidate adjunctive treatments should carefully consider and avoid known drug–drug interactions, such as those involving celecoxib and dexamethasone. Further clinical studies of the identified treatments targeting mast cells and/or histamine receptors in COVID-19 patients associated with clinical benefits are therefore strongly recommended.

Abstract Background Viruses such as Ebola, Marburg, influenza, mpox, MERS-CoV, SARS-CoV, and SARS-CoV-2 pose a significant risk for future pandemics. Developing novel antiviral medicines can be time-consuming and resource intensive. Repurposing existing medicines with antiviral activity offers a faster, cost-effective strategy to expand treatment options during public health emergencies. This scan aimed to identify and synthesise recent evidence on repurposed antiviral medicines under investigation for these viruses. Method A horizon scanning approach was employed, starting with a targeted search in Embase, followed by a systematic search of ClinicalTrials.gov to capture the developmental stages of the technologies. Eligible technologies included UK- or EU-licensed medicines repurposed as antiviral therapies for the viruses of interest. Vaccines, unlicensed medicines, and already approved treatments for the targeted viruses were excluded. Results A total of 196 repurposed technologies targeting the viruses were identified from published literature, and the expanded search on the clinical trials registry yielded 58 technologies in active clinical development. Interventional clinical trial activity was limited to influenza and COVID-19, with 29 technologies for COVID-19 and two for influenza advancing to phase III evaluation. For other viruses, proposed antiviral candidates were identified in the literature but had not progressed into clinical development. Commonly investigated pharmacological classes included direct-acting antivirals, tyrosine kinase inhibitors, immunomodulators, and anti-inflammatory agents. Conclusion Repurposing antiviral medicines represents a pragmatic strategy for rapid therapeutic deployment against emerging viral threats. Collaboration among researchers, policymakers, research funders, and regulatory bodies will be essential to improve pandemic preparedness and support repurposing efforts in emergency situations.