Open Source Repurposing Reveals Broad-Spectrum Antiviral Activity of Diphenylureas
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.
Authors
- Laura Riva (ORCID: https://orcid.org/0000-0003-2414-7341)
- Yong-Dae Gwon (ORCID: https://orcid.org/0000-0002-0703-4188)
- S. Lindemann (ORCID: https://orcid.org/0000-0002-0885-6175)
- Case W. McNamara (ORCID: https://orcid.org/0000-0002-5754-3407)
- Robert D. Damoiseaux (ORCID: https://orcid.org/0000-0002-7611-7534)
- Robert Garces
- Magnus Evander (ORCID: https://orcid.org/0000-0001-6034-4807)
- Vaithilingaraja Arumugaswami (ORCID: https://orcid.org/0000-0002-6872-5118)
- Mikael Elofsson (ORCID: https://orcid.org/0000-0002-3219-4669)
- Melanie G. Kirkpatrick (ORCID: https://orcid.org/0009-0008-4335-5342)
- Mårten Strand
- Ulrich Betz (ORCID: https://orcid.org/0000-0002-2355-7974)
- Brigitte N. Gomperts (ORCID: https://orcid.org/0000-0002-1809-723X)
- Amal Gebara-Lamb (ORCID: https://orcid.org/0009-0003-2271-3116)
- Norbert Beier (ORCID: https://orcid.org/0000-0001-8292-5928)
- Karen C. Wolff
Institutions
- Scripps Research Institute (US)
- University of California, Los Angeles (US)
- Merck KGaA, Darmstadt (Germany) (DE)
- Ono Pharmaceutical (United States) (US)
- Research & Development Institute (US)
- California Institute for Biomedical Research (US)
- Umeå University (SE)
Publication Details
- Journal
- Viruses
- Published
- 2025-03-07
- DOI
- https://doi.org/10.3390/v17030385
- Citations
- 1
- Primary Topic
- Respiratory viral infections research
- Type
- article
- Field-Weighted Citation Impact
- 1.35
Funders
- Bill and Melinda Gates Foundation
- Merck KGaA
- Vetenskapsrådet