Decoding the antiviral potential of eugenol, thymol and vanillin against human cytomegalovirus infection

Human cytomegalovirus (HCMV) poses serious health risks, particularly for immunocompromised individuals. However, the current FDA-approved anti-HCMV drugs face challenges such as drug resistance and significant side effects, underscoring the need for alternative treatment options. Essential oil components (EOCs), including eugenol, thymol and vanillin, are recognized for their therapeutic potential. This study evaluates their antiviral effects against HCMV in epithelial (ARPE-19) and fibroblast (MRC-5) cell lines. Among the EOCs, vanillin demonstrated the highest efficacy, characterized by low toxicity and a high selectivity index in both cell types. Mechanistic differences were noted between the cell lines. In ARPE-19 cells, eugenol showed virucidal activity, inhibited viral entry and suppressed early gene expression (IE-1). Conversely, in MRC-5 cells, eugenol mainly blocked viral entry and exhibited virucidal effects. Thymol was most effective in ARPE-19 cells, where it completely suppressed IE-1 expression as a result of both inhibition of viral entry and a direct disruptive effect on IE-1 expression. In addition, thymol showed an effect on viral replication. In MRC-5 cells, thymol primarily inhibited viral entry and attachment. Vanillin exhibited dual inhibitory activity in both cell lines, blocking viral attachment and entry. In MRC-5, vanillin also appears to affect intermediate processes. Notably, combining EOCs with ganciclovir resulted in synergistic effects. The eugenol/ganciclovir combination was particularly effective in ARPE-19 cells, while thymol/ganciclovir showed enhanced efficacy in MRC-5 cells. These findings suggest that EOCs have significant potential as adjunct therapies to improve antiviral outcomes and address drug-resistant HCMV strains.