A naturally produced peptide may quietly interfere with influenza viruses at one of their most critical steps, limiting infection before it begins.

A team led by the Fisabio Foundation has discovered that dermcidin, a peptide the human body continuously produces, can do more than fight bacteria and fungi. It also shows antiviral activity against influenza. The researchers found that people who remain free of flu-like symptoms tend to have higher baseline levels of dermcidin, suggesting it may help reduce the risk of infection.

The study included contributions from CIBERESP, the Institute of Biomedicine of Valencia (IBV-CSIC), CIBERER, the Institute of Research, Development and Innovation in Healthcare Biotechnology of Elche (IDiBE) at Miguel Hernández University, the University of Valencia, and the Margarita Salas Biological Research Center (CIB-CSIC), along with other national and international institutions.

“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 the 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,” adds Dr. Álex Mira, a Fisabio researcher and head of the Oral Microbiome group, who co-led the work.

A completely new mechanism of action

The researchers found that dermcidin targets hemagglutinin, a protein the influenza virus needs to enter cells, by attaching to a critical and highly conserved region involved in membrane fusion. This binding changes the protein’s structure, preventing the virus from fusing with the cell membrane and starting an infection. As a result, dermcidin can neutralize the virus before it gains entry, revealing a previously unknown way of blocking infection.

This approach differs from most current antivirals, which focus on neuraminidase, another viral protein that is increasingly showing resistance to treatment.

“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.

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.”

Present in the nose, saliva, and tears

In addition to sweat, dermcidin was detected in key entry points for respiratory viruses, including 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.

Toward new antiviral treatments

The findings point to dermcidin as a promising candidate for future antiviral therapies. Beyond directly blocking viruses, researchers are also exploring whether it helps regulate immune responses during infection.

By focusing on stable regions of viruses that rarely change, dermcidin-based approaches could lower the risk of drug resistance and improve effectiveness against a wide range of respiratory viruses.