Shahrekord University of Medical Sciences Future Natural Products 2783-4662 11 1 2026 10 20 Synergistic Effects of Acyclovir and Curcumin on Herpes Simplex Virus Type 1 4 9 10.34172/fnp.322 EN Maryam Reisi https://orcid.org/0000-0002-1880-5240 Masoud Hafizi https://orcid.org/0000-0001-8003-9041 Pegah Khosravian https://orcid.org/0000-0002-4802-8534 Dhiya Altememy https://orcid.org/0000-0003-0311-9827 Fatemeh Javadi-Farsani https://orcid.org/0000-0002-3269-9704 Mohammad-Taghi Moradi https://orcid.org/0000-0002-3103-3740 Journal Article 10.34172/fnp.322 2025 08 27 2025 10 26 Introduction: The emergence of drug-resistant viral strains has emphasized the need for natural antiviral compounds with fewer side effects. Curcumin, a natural polyphenol, exhibits antiviral, antioxidant, antitumor, and anti-inflammatory activities. Considering that drug combinations can reduce resistance development and cytotoxicity by lowering effective doses, this study aimed to evaluate the synergistic effects of curcumin combined with acyclovir against herpes simplex virus type 1 (HSV-1) in vitro. Methods: In this experimental study, the cytotoxicity of curcumin and acyclovir was assessed on Vero cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Moreover, the antiviral activity of curcumin and acyclovir alone, as well as acyclovir combined with the 10% cytotoxic concentration (CC10) of curcumin, was evaluated using MTT and 50% tissue culture infective dose assays, and the 50% inhibitory concentration (IC50) underwent calculation. Ultimately, synergistic effects were analyzed by determining viral growth inhibition percentages at various drug concentrations, and the combination index was computed using CompuSyn 1.0. Results: The CC50 values of acyclovir and curcumin were 537.7 µM and 74.44 µM, respectively. Furthermore, the IC50 values were 0.395, 12.6 µM, and 0.144 µM for acyclovir, curcumin, and the combination of acyclovir with 20 µM (CC10) curcumin, respectively. Both compounds significantly reduced viral titers individually and in combination. Finally, the combined treatment demonstrated a synergistic antiviral effect at the tested concentrations. Conclusion: Overall, curcumin had notable antiviral activity against HSV-1 in vitro and substantially enhanced acyclovir’s antiviral efficacy through synergistic interaction, suggesting potential for future clinical evaluations.