Antiviral activity of OFE against HSV-1. Different assays were performed in order to evaluate anti-HSV-1 activity. (A) Co-treatment: simultaneous addition of OFE and virus to the cells; (B) Virus pre-treatment: virus incubated with OFE and titrated on the cells; (C) Cell pre-treatment: OFE incubated with the cells before the viral infection; (D) Post-treatment: OFE added to the infected cells. OFE interfered with the early stages of infection acting in co-treatment (A) and virus pre-treatment (B) assays, although it was not able to interact with the cellular surface (C) or block the viral replication (D). Different compounds were used as the positive control (+) for each treatment: Greco grape cane extract [7] (A, B, 10 μg/mL for both the assays), dextran sulfate (C, 1 μM), and acyclovir (D, 5 μM), whereas infected cells were used as the negative control (−). Statistical analyses were determined by ANOVA with Dunnett’s test for multiple comparisons. Significances are referred to as the negative control (−). **** p < 0.0001; ns: non-significant.