A different purpose has attracted attention for treating skin damage rather than simply preventing it. Dermcidin was previously known as a skin protector. This antimicrobial peptide produced by our bodies may perform additional functions beyond simply acting as an antimicrobial agent against fungi and bacteria. In addition, these functions may include potentially acting on the potential for viruses to enter the body and cause illness.

Researchers at Fisabio have demonstrated that dermcidin can also protect against infection with the virus that causes the flu. It does this by interfering with its entry into the cell before it can infect the cell.

A very interesting angle to consider is that people with high levels of dermcidin at baseline, as shown in this study, have a lower likelihood of developing flu-like symptoms than do those with low levels. In the participants in this study who had no flu-like symptoms after exposure to the virus, the levels of dermcidin present were at least six times higher. These levels were higher than the levels present in the subjects who were infected.

This important finding adds a human element to the study. It indicates that an important part of the distinction between becoming ill and remaining symptom-free after exposure to a virus may come from the body’s ability to produce and utilize its own natural biochemical defenses.

How Dermcidin Blocks Infection

According to Dr. María D. Ferrer, researcher at Miguel Servet Institute and director of the Antimicrobial Peptides and Glycobiology group at Fisabio, "Dermcidin is present in sweat; in addition to being an antibacterial and antifungal, dermcidin has antiviral activity against the influenza virus and has been shown to prevent the infection of cells in both in vitro and in vivo models."

Contributing to the research were members of CIBERESP, the Institute of Biomedicine of Valencia (IBV-CSIC), CIBERER, the Institute of Research, Development and Innovation in Biotechnology of Elche (IDiBE) of the University Miguel Hernández. In addition, researchers from the University of Valencia, the Margarita Salas Biological Research Center (CIB-CSIC), and many other national and international research centers took part.

What makes dermcidin particularly interesting is the mechanism by which it works. The researchers determined that the peptide binds to hemagglutinin, a viral protein required for influenza to enter cells. Specifically, dermcidin binds to a region of hemagglutinin that is necessary for the fusion process.

This process allows the influenza virus to assimilate with the host cell membrane in order to initiate an infection.

Dermcidin to hemagglutinin

The binding action of dermcidin to hemagglutinin also alters the shape of the viral protein. Once that alteration occurs, the influenza virus loses its ability to perform the fusion step. This step is necessary for it to infect host cells.

Rather than thwarting the virus after it has begun to invade, dermcidin inhibits the influenza virus earlier in the infection trajectory. This happens before the virus has a chance to establish a foothold in the host cell.

The action of dermcidin is different from that taken by the majority of current antiviral medications for influenza. Most antivirals target neuraminidase. However, resistance to many neuraminidase inhibitors is already emerging, thereby increasing the urgency in finding new strategies to combat influenza.

Why Baseline Levels Matter

According to Dr. Ferrer, "by targeting regions of the virus that are maintained relatively unchanged across different viral subtypes (i.e., highly conserved regions), dermcidin could offer protection against the many different strains of the influenza virus." This is particularly important because regions of the virus that are highly conserved usually remain relatively stable as the influenza virus undergoes other changes. The presence of dermcidin on the skin and in the body represents an opportunity for the innate immune system's first line of defense against viral respiratory infections.

In addition to sweat, dermcidin has been identified as a molecule associated with dermal and respiratory infection entry sites. It is also present in the nasopharynx, saliva, and tears. These anatomical locations are locations where the innate immune system initially attempts to stop a respiratory virus from entering the body.

"The data indicate that dermcidin levels are between two and 10 times greater in the non-symptomatic than in the symptomatic individuals," said Dr. Paula Corell, the lead author of the study and a member of the research team.

The research team found that dermcidin levels increased with respiratory infection. This further supports that dermcidin is a component of the innate immune system. Dermcidin potentially acts as a rapidly activated and built-in response system for the body.

Broader Antiviral Potential

"Together, the results confirm that dermcidin is an important component of the innate immune system's early response to a virus," stated Dr. Corell.

Beyond influenza symptoms in people, dermcidin has been shown to protect mice against disease caused by influenza A virus. It also demonstrated broad antiviral activity against multiple strains of influenza A virus and many respiratory virus types in vitro.

Researchers think the same principles behind dermcidin's ability to stop the flu virus from replicating may also apply to other respiratory viruses as well. In addition, because dermcidin has specific sites or regions that other viruses share, it has great promise as an antiviral compound against multiple viruses.

Peptide research has previously demonstrated antiviral properties against unrelated viruses such as measles and OC43, the most common cause of acute respiratory infections. While this does not suggest dermcidin is currently ready for broad-spectrum antiviral therapy, it creates the opportunity that the functions of dermcidin could be extended beyond the flu. This opportunity may make it useful for many different viruses.

What This Could Mean for Future Treatments

According to Dr. Álex Mira, senior researcher with Fisabio and leader of the group on the oral microbiome, "the same principles apply to other respiratory viruses such as measles, common coronaviruses, and perhaps others. This raises the possibility for a broader-spectrum effect."

Dr. Mira notes the new findings underscore an important larger point, beyond just a single molecule or virus. "The results here tell us our own bodies produce natural processes capable of stopping viruses, thus paving the way for the development of new, more effective antivirals," says Dr. Mira. Researchers are studying the potential for dermcidin to regulate the body’s immune response as well. Therefore, dermcidin may act as an immunomodulatory agent. It influences the body's immune response while also inhibiting viral replication.

Continued research on the above topics is under way.

The findings of this study point to a new way of thinking about developing antiviral therapeutics. Rather than solely targeting viral proteins already known to be resistant to drugs, researchers will be able to utilize naturally occurring human-derived molecules like dermcidin as potential therapeutic agents.

A New Direction for Antiviral Therapeutics

Dermcidin has unique characteristics that set it apart from other types of antiviral compounds available today for the treatment of viral illnesses: it acts to inhibit viral infection before a virus can enter the host cell. It targets a highly conserved region of most viruses. Furthermore, it is expressed at the first point of entry into the respiratory tract.

The fact that the expression of dermcidin occurs in healthy individuals who do not exhibit signs of influenza infection suggests that differences in dermcidin expression levels may play a role in the ability of some individuals to resist influenza infection.

If future studies replicate the findings of this work, dermcidin holds promise as a candidate for developing both preventative and therapeutic strategies to combat respiratory viral infections. Furthermore, dermcidin may lead to new classes of antiviral drugs. These drugs will be more difficult to develop resistance to. Therefore, they will be effective against many different flu strains and perhaps other respiratory viruses.