Assessment of The Broad-Spectrum Host Targeting Antiviral Efficacy of Halofuginone Hydrobromide in Human Airway, Intestinal and Brain Organoid Models.

Abstract Halofuginone hydrobromide has shown potent antiviral efficacy against a variety of viruses such as SARS-CoV-2, dengue, or chikungunya virus, and has, therefore, been hypothesized to have broad-spectrum antiviral activity. In this paper, we tested this broad-spectrum antiviral activity of Halofuginone hydrobomide against viruses from different families ( Picornaviridae, Herpesviridae, Orthomyxoviridae, Coronaviridae, and Flaviviridae). To this end, we used relevant human models of the airway and intestinal epithelium and regionalised neural organoids. Halofuginone hydrobomide showed antiviral activity against SARS-CoV-2 in the airway epithelium with no toxicity at equivalent concentrations used in human clinical trials but not against any of the other tested viruses. Graphical abstract Highlights Halofuginone hydrobromide was identified as a possible broad-spectrum host targeting antiviral drug. Human organoid models offer a physiologically relevant and clinically translatable model for antiviral research. Halofuginone hydrobromide shows antiviral efficacy against SARS-CoV-2, but not against EV-A71, PeV-A1, IAV, RV-A16, HCMV or ZIKV in relevant organoid models. The efficacy of Halofuginone hydrobromide is concentration dependent as well as on proline content of the host receptor(s) or host factors for the specific virus in question.