Abstract

Herpes simplex viruses are double-stranded DNA viruses known to cause numerous diseases, such as skin lesions in the oro-facial area, herpetic gingivostomatitis, herpetic keratitis, and encephalitis, among others. The antiviral acyclovir is commonly used for systemic and topical treatment of HSV but is poorly effective in treating skin lesions, and several clinical studies have reported resistance in the immunosuppressed. Cetylpyridinium chloride (CPC) is a quaternary ammonium compound that is a cationic surfactant and has been previously described to have antimicrobial (fungicidal and bactericidal) properties. More recently, it was shown to hamper influenza virus infection. Here, we evaluated the potential antiviral properties for CPC against herpes simplex viruses type 1 and type 2 (HSV-1 and HSV-2) in primary human gingival fibroblasts. We used an HSV-1 virus that expresses a green fluorescent protein (GFP) in the form of a fusion protein with the viral capsid protein VP26 and an HSV-2 virus that encodes a non-structural form of GFP. To evaluate the cytotoxic activity of CPC and its effect on cell viability, we used the fluorescent redox indicator resazurin. We found that CPC displays antiviral activity against HSV-1 and HSV-2, notably when applied after infection. Importantly, CPC reduced virus plaque formation, virus-encoded viral protein expression (glycoprotein B and glycoprotein D), decreased the expression of a reporter gene encoded within the genome (GFP) and reduced the presence of viral genomes in infected cells (qPCR). The antiviral effects of CPC was accompanied by low cytotoxic effects in primary human gingival fibroblast. Taken together, CPC has antiviral effects over HSV, different from a virucidal activity. Our data suggest that CPC likely affects early events in the replication cycle of HSV. However, additional experiments are needed to determine the exact mechanism of action of CPC against HSV.