Enhancement of anti-herpetic activity of glycyrrhizic acid by physiological proteins

Some enzymes present in biological fluids, such as lysozyme (LYS) and lactoferrin (LAC), are known to possess antibacterial and antiviral activity, against herpesviruses in particular. It will be shown in this paper that their combination with a natural triterpene, namely glycyrrhizic acid (GLA), gives significant results in enhancing the antagonistic activity on HSV1 in in vitro assays. Data elaboration was carried out by calculation of the FIC index (fractional inhibitory concentration) for each combination of the three compounds and by a three-dimensional evaluation of the inhibiting combinatory effects, which indicated the percentage of the synergistic action. A FIC index equal to or below 0.5 demonstrated a significant synergistic effect between two substances. Considering each single compound, the 50% inhibiting doses on viral replication (ID50) were 252+/-53 mug/ml for LAC, 497+/-165 mug/ml for LYS and 740+/-125 mug/ml for GLA. The combination of LAC and GLA showed a clear synergistic effect, with a FIC index of 0.08 and a potentiating activity which, for some doses, was up to 1.5 log(10) of difference (from about 5.5 x 10(6) to 10(5) pfu/ml). The combinations of GLA and LYS, and LYS and LAC showed a less significant synergistic activity. These findings led to the conclusion that some physiological proteins, even at concentrations usually present in some body fluids, may enhance the anti-herpetic activity of a natural compound such as GLA.