Natural peptide in sweat may help block flu infection before symptoms start

A naturally produced peptide found in sweat, saliva, tears, and the nasopharynx may help stop influenza before it takes hold, offering a promising new path toward antivirals that target conserved viral weak points with less risk of resistance.

A research team led by the Fisabio Foundation has demonstrated that dermcidin, a constitutively produced antimicrobial peptide, also exhibits antiviral activity against the influenza virus. The study also shows that people who do not develop flu-like symptoms have higher baseline levels of this molecule, which could be associated with lower susceptibility to infection.

Researchers from CIBERESP, the Institute of Biomedicine of Valencia (IBV-CSIC), and CIBERER, the Institute of Research, Development and Innovation in Healthcare Biotechnology of Elche (IDiBE) of the University Miguel Hernández, the University of Valencia, and Margarita Salas Biological Research Center (CIB-CSIC), among other national and international centers,s have also contributed to the study.

"Dermcidin, which is present in sweat and known for its antibacterial and antifungal activity, also exhibits antiviral activity against the influenza virus and can interfere with infection, as we have observed in in vitro and in vivo models", explains Dr. María D. Ferrer, Miguel Servet researcher and head of the Antimicrobial Peptides and Glycobiology group at Fisabio, who led this study.

"These results show that our own bodies have natural mechanisms capable of curbing viral infection, which opens the door to the development of new, more effective antivirals", notes Dr. Álex Mira, researcher at Fisabio and head of the Oral Microbiome group, who co-directed the study.

Dermcidin Blocks Influenza Cell Entry

The study has demonstrated that dermcidin binds to hemagglutinin, a protein essential for the influenza virus to enter the cell, at a key, highly conserved region involved in the fusion process. This interaction induces a conformational change in the viral protein that impairs the virus's ability to fuse with the cell membrane and, therefore, initiate infection. In this way, dermcidin inactivates the virus before it can infect the cell, through a previously unknown mechanism of action.

This mode of action contrasts with that of most available antivirals, which target neuraminidase, another viral protein, and against which resistance is emerging.

"By acting on regions of the virus that hardly change between subtypes-known as highly conserved regions-dermcidin could contribute to defense against different variants of the influenza virus", explains Dr. Ferrer.

In this sense, Dr. Mira adds that "this same principle could be extended to other respiratory viruses, such as the measles virus and coronaviruses associated with the common cold, suggesting a possible broad-spectrum effect."

Dermcidin Levels in Respiratory Tissues

The team has found that dermcidin is present not only in sweat but also in the main entry points for respiratory viruses into the body, such as the nasopharynx, saliva, and tears.

"The results show that baseline levels of dermcidin are up to six times higher in people who do not develop flu-like symptoms, compared to susceptible individuals", explains Dr. Paula Corell, the study's first author and a member of the team. Furthermore, during a respiratory infection, its concentration increases significantly. "Altogether, these findings reinforce the idea that dermcidin is part of the innate immune system's first line of defense against this type of infection," adds Dr. Corell.

Broad-Spectrum Antiviral Treatment Potential

Researchers note that dermcidin is a promising candidate for developing new strategies to combat respiratory viral infections. In addition to its direct antiviral activity, the team is investigating whether dermcidin may also play an immunomodulatory role, helping regulate the immune system's response to infection.

These findings open new research avenues for the development of antivirals based on the body's natural molecules that target highly conserved viral regions, thereby reducing the likelihood of resistance and enhancing their effectiveness against various respiratory viruses.

Funding Support for Dermcidin Research

This research has received funding from the Valencian Innovation Agency (AVI) through grants INNVAL20/18/005 and INNVAL20/19/006, as well as the INNVA2/2021/3 grant, also funded by the Valencian Innovation Agency (AVI) and the European Union through the European Regional Development Fund (ERDF). Moreover, this research has received support from the Carlos III Health Institute (ISCIII), under grant code CP22/00036, based on the Resolution of the Directorate of the Carlos III Health Institute, O.A., M.P., dated December 7, 2022, granting Miguel Servet contracts and additional grants, and co-funded by the European Union. The study has also been funded by the Ministry of Economy and Competitiveness through file SAF2013-505553-EXP.

Source:

• Universidad Miguel Hernandez de Elche

Journal reference:

• Corell-Escuin, P., Belmonte-Ballester, S., Adhav, A., Marina, A., Gadea-Salom, L., Martinez-Gil, L., Aledavood, E., Fernández-Escamilla, A. M., Gómez Sáez, A., Gougeard, N., Dee, K., Murcia, P. R., Magos, E. A., Llena, C., Peris-Martínez, C., Artacho, A., Mengual-Chuliá, B., López-Labrador, F. X., Mira, A., . . . Ferrer, M. D. (2026). Dermcidin has antiviral activity and protects against influenza. Proceedings of the National Academy of Sciences, 123(14), e2424461123. DOI: 0.1073/pnas.2424461123, https://www.pnas.org/doi/pdf/10.1073/pnas.2424461123