Open Source Repurposing Reveals Broad-Spectrum Antiviral Activity of Diphenylureas
2025
Ulrich A. K. Betz | Robert Garces | Norbert Beier | Sven Lindemann | Karen C. Wolff | Laura Riva | Melanie G. Kirkpatrick | Amal Gebara-Lamb | Case W. McNamara | Robert Damoiseaux | Brigitte N. Gomperts | Vaithilingaraja Arumugaswami | Mårten Strand | Yongdae Gwon | Mikael Elofsson | Magnus Evander
The pandemic threat from newly emerging viral diseases constitutes a major unsolved issue for global health. Antiviral therapy can play an important role in treating and preventing the spread of unprecedented viral infections. A repository of compounds exhibiting broad-spectrum antiviral activity against a series of different viral families would be an invaluable asset to be prepared for future pandemic threats. Utilizing an open innovation crowd-sourcing paradigm, we were able to identify a compound class of diphenylureas that exhibits in vitro antiviral activity against multiple viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), adenovirus, dengue virus, herpes, and influenza viruses. Compound 4 among the series exhibits strong activity against dengue virus, a growing global health problem with high medical need and no approved antiviral drug. The compounds are active against SARS-CoV-2 in a primary human stem cell-based mucociliary airway epithelium model and also active in vivo, as shown in a murine SARS-CoV-2 infection model. These results demonstrate the potential of the chemical class as antivirals on the one hand and the power of open innovation, crowd-sourcing, and repurposing on the other hand.
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