Abstract
Herpesvirus infections represent a global medical and social problem: according to WHO data, approximately 3.8 billion people are infected with herpes simplex virus type 1 (HSV-1), while the prevalence of HSV-2 amounts to about 520 million cases. Despite the wide application of acyclovir (ACV) and its analogues as standard therapy, their effectiveness is limited by increasing drug resistance, nephrotoxicity, and inability to completely eliminate the virus. Therefore, searching for new therapeutic strategies, including combination drugs based on natural compounds, remains a topical issue. The aim of this study was to justify the feasibility of combining glycyrrhizinic acid (GA), the main active ingredient of licorice root, with synthetic antiviral agents to create a combined medication with enhanced efficiency and reduced toxicity. GA exhibits potent antiviral activity against HSV-1 and HSV-2, inhibiting viral replication during penetration and virion assembly stages, disrupting interactions between viral proteins and cellular receptors, and downregulating expression of early viral proteins (ICP0, ICP4). Moreover, GA modulates immune response by enhancing interferon activity and natural killer (NK) cell activation, while also decreasing levels of proinflammatory cytokines (IL-6, TNF-α), thereby alleviating inflammatory manifestations of herpetic infection.