Elaeocarpus sylvestris var. ellipticus Extract and Its Major Component, Geraniin, Inhibit Herpes Simplex Virus-1 Replication

Elaeocarpus sylvestris var. ellipticus (ES), which our research group had confirmed inhibits influenza A and SARS-CoV-2 viruses, was investigated to identify new potent and selective inhibitors of herpes simplex virus-1 (HSV–1) replication. To clarify the optimal condition for ES extract (ESE), ES was extracted at different concentrations of 0, 30, 50, 70, and 100%, to screen for its anti-HSV–1 effect. Among these ESE samples, ESE50 (50% concentration) exhibited the strongest inhibition of HSV–1 replication (EC₅₀ 23.2 μg/mL) while showing low cytotoxicity on host cells (IC₅₀ 342.8 μg/mL). The treatment of ESE50 clearly demonstrated a decrease in the expression of ICP0 in the lungs of HSV–1-infected BALB/c nude mice, compared to the MOCK group. Geraniin, which was isolated from ESE50 and analyzed using ESI−MS and 1D−(¹H− and ¹³C−) and 2D−NMR, showed greater potency in inhibiting HSV–1 replication, as determined by the plaque reduction assay (EC₅₀ 8.3 μg/mL) and luciferase inhibition (EC₅₀ 36.9 μg/mL). The results demonstrate that ESE50 and geraniin show great potential as candidates for new drug discovery in the treatment of HSV–1 and related diseases.