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

Garcia-Rodriguez, I.; Moreni, G.; Capendale, P. E.; Aknouch, I.; Mulder, L. A.; Johannesson, N.; Vieira de Sa, R.; Freeze, E.; van Eijk, H.; Koen, G.; Wolthers, K. C.; Pajkrt, D.; Sridhar, A.; Calitz, C.

doi:10.1101/2023.11.01.565121

bioRxiv · 10.1101/2023.11.01.565121

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

Garcia-Rodriguez, I.·Moreni, G.·Capendale, P. E.·Aknouch, I.·Mulder, L. A.·Johannesson, N.·Vieira de Sa, R.·Freeze, E.·van Eijk, H.·Koen, G.·Wolthers, K. C.·Pajkrt, D.·Sridhar, A.·Calitz, C.

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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 O_FIG O_LINKSMALLFIG WIDTH=199 HEIGHT=200 SRC="FIGDIR/small/565121v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@10d562eorg.highwire.dtl.DTLVardef@94f903org.highwire.dtl.DTLVardef@683b6forg.highwire.dtl.DTLVardef@11620ba_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIHalofuginone hydrobromide was identified as a possible broad-spectrum host targeting antiviral drug. C_LIO_LIHuman organoid models offer a physiologically relevant and clinically translatable model for antiviral research. C_LIO_LIHalofuginone 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. C_LIO_LIThe 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. C_LI

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Garcia-Rodriguez, I., Moreni, G., Capendale, P. E., Aknouch, I., Mulder, L. A., Johannesson, N., Vieira de Sa, R., Freeze, E., van Eijk, H., Koen, G., Wolthers, K. C., Pajkrt, D., Sridhar, A., Calitz, C.. 2023-11-01. Assessment of The Broad-Spectrum Host Targeting Antiviral Efficacy of Halofuginone Hydrobromide in Human Airway, Intestinal and Brain Organoid Models.. https://doi.org/10.1101/2023.11.01.565121

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