Dermcidin has antiviral activity and protects against influenza.
Despite the large incidence of influenza virus infections, one-fifth of influenza-infected individuals remain resistant to developing symptoms. By screening genetic libraries from asymptomatic individuals, we have discovered that the human antimicrobial peptide (AMP) dermcidin has antiviral activity against the influenza virus in a strain- and subtype-dependent manner. The dermcidin-derived peptide DCD-1L binds the viral hemagglutinins, thereby interfering in the first phase of the viral infection cycle and it shows potential antiviral activity against respiratory viruses with hemagglutinin-like envelope proteins. We demonstrate that dermcidin is produced in all entry routes of respiratory viruses into the human body (saliva, nasopharynx, and tears), and its levels increase during viral respiratory infections. In addition, asymptomatic individuals had larger dermcidin levels than susceptible ones, suggesting its role in the resistance to developing respiratory symptoms. We confirm that this human AMP inhibits influenza virus infection in vitro and in vivo, highlighting its potential as a new natural drug for the prevention and treatment of viral respiratory infections.