Therapeutic Potential of Glycyrrhiza glabra (Licorice) Against COVID-19: Mechanistic Insights and Technological Advances from In Silico, Preclinical and Clinical Evidence

Abstract

Glycyrrhiza glabra L. (licorice), renowned in ethnopharmacology, harbors bioactive metabolites such as glycyrrhizin, liquiritin, and flavonoids that confer antiviral, anti-inflammatory, antioxidant, and immunomodulatory properties pertinent to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This review appraises in vitro, in silico , preclinical, and clinical data, revealing glycyrrhizin’s potent inhibition of SARS-CoV-2 main protease (Mpro; EC50 ≈ 0.44 mg/mL in Vero E6 cells) and disruption of envelope protein lipid interactions, alongside suppression of cytopathic effects and plaque formation. Anti-inflammatory efficacy stems from downregulated nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and cytokines (tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6)), mitigating cytokine storms, while immunostimulant effects include T-/B-lymphocyte proliferation and natural killer cell activation. Preliminary randomised trials (n=20-70) in mild-moderate coronavirus disease 2019 (COVID-19) demonstrate symptom alleviation (cough, dyspnea; p <0.05) with root extracts (700-760 mg/day), though severe cases warrant larger validations addressing glycyrrhizin-induced hypokalemia risks. These findings advocate licorice as an adjunctive therapeutic candidate, pending optimised formulations. Furthermore, advanced technological approaches including in silico modelling, molecular docking, and computational target prediction have accelerated the identification of licorice-derived bio-actives and their therapeutic targets against SARS-CoV-2.