Enhancing the solubility of SARS-CoV-2 inhibitors to increase future prospects for clinical development
Despite the existence of vaccines for SARS-CoV-2, the constant evolution of new variants and the occurrence of breakthrough infections highlight the need for new and effective antiviral approaches. We have shown that lipopeptides designed to bind a conserved region on the SARS-CoV-2 spike protein can effectively block viral entry into cells and thereby block infection. To support the feasibility of using this approach in humans, we re-designed these lipopeptides to be more soluble, using information about the structure of the spike protein interacting with the peptides to modify the peptide chain. The new peptides are effective against both SARS-CoV-2 and MERS. The lipopeptides described here could serve as treatment for people who are unvaccinated or who experience breakthrough infections, and the approach to increasing solubility can be applied in a broad spectrum approach to treating infections with emerging viruses.
Authors
- Megan C. Mears (ORCID: https://orcid.org/0000-0003-1293-7696)
- Ariel J. Kuhn (ORCID: https://orcid.org/0000-0003-1535-8614)
- Zhen Yu (ORCID: https://orcid.org/0000-0003-2092-9960)
- Victor K. Outlaw (ORCID: https://orcid.org/0000-0001-7054-4204)
- Dale F. Kreitler (ORCID: https://orcid.org/0000-0003-4758-7913)
- Samuel H. Gellman (ORCID: https://orcid.org/0000-0001-5617-0058)
- Dennis A. Bente (ORCID: https://orcid.org/0000-0002-5150-7368)
- Jennifer Mook
- Matteo Porotto (ORCID: https://orcid.org/0000-0003-3866-9220)
- Anne Moscona (ORCID: https://orcid.org/0000-0002-1796-8320)
- Tara C. Marcink (ORCID: https://orcid.org/0000-0003-4295-1229)
- Maria N.B. Cajimat
- Payton R. Cleven
Institutions
- University of Wisconsin–Madison (US)
- University of Campania "Luigi Vanvitelli" (IT)
- Brookhaven National Laboratory (US)
- Columbia University Irving Medical Center (US)
- The University of Texas Medical Branch at Galveston (US)
Publication Details
- Journal
- Journal of Virology
- Published
- 2025-02-04
- DOI
- https://doi.org/10.1128/jvi.02159-24
- Citations
- 2
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 2.79
Funders
- U.S. Department of Energy
- National Institutes of Health
- Office of Science
- Vagelos College of Physicians and Surgeons, Columbia University
- National Institute of General Medical Sciences
- National Institute of Allergy and Infectious Diseases
- Basic Energy Sciences
- Biological and Environmental Research
- Brookhaven National Laboratory