Unveiling Ranalexin-1G activity against polymicrobial skin infections.

OBJECTIVES: Skin and mucosal viral infections caused by Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), often complicated by opportunistic bacteria such as Staphylococcus epidermidis (S. epidermidis), represent a significant clinical challenge. Increasing resistance to conventional antivirals and antibiotics underscores the urgent need for alternative therapies. Here, Ranalexin-1G, an amphibian-derived antimicrobial peptide (AMP) from Rana grylio, was investigated for its antiviral and antibacterial properties. METHODS: Ranalexin-1G was evaluated for its antiviral activity by plaque reduction assay and qPCR. Antibacterial activity against S. epidermidis was assessed by measuring growth inhibition and minimum inhibitory concentration (MIC) values for both reference and clinical strains. In addition, an in vitro co-infection model (HSV-1 + S. epidermidis) in HaCaT keratinocytes was used to examine the peptide dual functionality. RESULTS: Ranalexin-1G exhibits a dual activity: it demonstrates potent antiviral effects against HSV-1, HSV-2, and an acyclovir-resistant HSV-1 strain, with half-maximal inhibitory concentration (IC50) values ranging from 3 to 10 μM. Additionally, Ranalexin-1G shows strong antibacterial activity, achieving 90% inhibition of S. epidermidis growth, with minimum inhibitory concentration (MIC) values of 3.125 and 6.25 μM for the reference and clinical strains, respectively. Consistent with these findings, in an in vitro co-infection model of HSV-1 and S. epidermidis in HaCaT cells, Ranalexin-1G significantly reduced bacterial invasion. CONCLUSIONS: Overall, Ranalexin-1G emerges as a promising candidate for the treatment of polymicrobial skin infections, particularly those involving viral-bacterial co-infections, due to its balanced efficacy and low cytotoxicity profile.