Several
essential oils exert in vitro activity against bacteria and viruses and, among these latter, herpes simplex virus type 1 (HSV-1) is known to develop resistance to commonly used
antiviral agents. Thus, the effects of the
essential oil derived from Mentha suaveolens (EOMS) and its active principle
piperitenone oxide (PEO) were tested in in vitro experimental model of
infection with HSV-1. The 50% inhibitory concentration (IC50) was determined at 5.1μg/ml and 1.4μg/ml for EOMS and PEO, respectively. Australian
tea tree oil (TTO) was used as control, revealing an IC50 of 13.2μg/ml. Moreover, a synergistic action against HSV-1 was observed when each oil was added in combination with
acyclovir. In order to find out the mechanism of action, EOMS, PEO and TTO were added to the cells at different times during the virus life-cycle. Results obtained by yield reduction assay indicated that the
antiviral activity of both compounds was principally due to an effect after viral adsorption. Indeed, no reduction of virus yield was observed when cells were treated during viral adsorption or pre-treated before
viral infection. In particular, PEO exerted a strong inhibitory effect by interfering with a late step of HSV-1 life-cycle. HSV-1
infection is known to induce a pro-oxidative state with depletion of the main intracellular
antioxidant glutathione and this redox change in the cell is important for viral replication. Interestingly, the treatment with PEO corrected this deficit, thus suggesting that the compound could interfere with some redox-sensitive cellular pathways exploited for viral replication. Overall our data suggest that both EOMS and PEO could be considered good candidates for novel anti-HSV-1 strategies, and need further exploration to better characterize the targets underlying their inhibition.