Abstract
Background and aims: The emergence of drug-resistant viral strains has highlighted the importance of discovering natural compounds with antiviral properties and fewer side effects. Curcumin, a natural polyphenol, exhibits various pharmacological effects, including antiviral, antioxidant, antitumor, and anti-inflammatory activities. Since drug combinations reduce the likelihood of resistance mutations and also minimize cytotoxicity by lowering the required drug concentrations, this study aimed to investigate the synergistic effect of curcumin in combination with acyclovir against herpes simplex virus type 1 (HSV-1) in vitro. Methods: In this experimental study, the cytotoxicity of curcumin and acyclovir was evaluated on VERO cells using the MTT assay. Antiviral activity of curcumin and acyclovir alone and the combination of acyclovir with CC10 concentration of curcumin on HSV-1 virus was determined by MTT and TCID50 methods and a concentration that had 50% viral inhibition (IC50) was calculated. To assess synergism, the percentage of viral growth inhibition at various concentrations of curcumin and acyclovir, alone and in combination, was analyzed, and the Combination Index (CI) was calculated using Compusyn software. Results: The CC50 values of acyclovir and curcumin were 537.7µM and 74.44µM, respectively. The IC50 values were 0.395µM for acyclovir, 12.6µM for curcumin, and 0.144µM for the combination of acyclovir with 20 µM (CC10) curcumin. Both acyclovir and curcumin alone, as well as their combination, significantly reduced viral titers. The concurrent use of acyclovir and curcumin exhibited a synergistic effect at the tested concentrations. Conclusion: The findings of this study demonstrated that curcumin possesses significant antiviral potential against HSV-1 in vitro. The combined use of curcumin and acyclovir significantly improved the antiviral potency of acyclovir via a synergistic interaction, indicating its potential as an effective therapeutic approach for future clinical studies.