Glycyrrhetinic acid, a bioactive compound derived from glycyrrhizin in licorice root (Glycyrrhiza glabra), has been investigated for its potential antiviral properties, including activity against herpes simplex virus (HSV), the causative agent of cold sores. In vitro studies have demonstrated that glycyrrhetinic acid and related licorice extracts can inhibit replication of HSV-1, the primary virus responsible for cold sores, by disrupting viral gene expression and interfering with viral attachment to host cells. One study (Pompei et al., 1979, Nature) showed inhibition of HSV-1 and HSV-2 by glycyrrhizic acid and glycyrrhetinic acid in cell cultures.

However, clinical evidence in humans is limited. Some topical formulations containing glycyrrhetinic acid are marketed for cold sore relief, and a few small clinical trials suggest modest benefit in reducing healing time or symptom severity, but these studies are generally low quality, with small sample sizes and lack of robust controls. Systematic reviews and meta-analyses on the subject are lacking, and more rigorous clinical data are needed to confirm efficacy and safety.

In summary, glycyrrhetinic acid demonstrates scientific potential as an anti-HSV agent based on laboratory studies, with limited but suggestive clinical evidence for supporting its use in cold sores. The overall evidence is rated as weak to moderate (2/5) due to the paucity of high-quality clinical trials.