Therapeutic Potential of
Glycyrrhiza glabra
(Licorice) Against COVID-19: Mechanistic Insights and Technological Advances from In Silico, Preclinical and Clinical Evidence
Jul 2026· Science and Technology Nexus· pp. 1-7· 0 citations· 29 references
TL;DR
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 and these findings advocate licorice as an adjunctive therapeutic candidate, pending optimised formulations.
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.
C. nutans demonstrates significant medicinal potential, and future research priorities should include bioactivity-guided isolation of novel metabolites, validated in vivo mechanistic studies, pharmacokinetic and metabolomic profiling, and the implementation of standardized Phase I/II clinical trials and veterinary evaluations to support its further development and application.
Wenxuan Si, Xinyue Sun, Yuanbin Han et al.· Frontiers in Pharmacology· 0 citations
Carpione rhabdovirus 2023 (CAPRV2023) is an emerging, highly pathogenic pathogen infecting Golden pompano (Trachinotus anak), capable of triggering mass mortality in marine aquaculture populations and causing severe economic losses. Berberine (BBR) and glycyrrhetinic acid (GA) are natural active compounds classified as an isoquinoline alkaloid and a pentacyclic triterpenoid, respectively, both of which are widely utilized in traditional medicine owing to their antiviral, anti-inflammatory, and hepatoprotective properties. In this study, the combined therapeutic efficacy of the BBR and GA combination against CAPRV2023 infection was systematically evaluated at both in vitro and in vivo levels, with the underlying mechanistic pathways of its protective effects further comprehensively investigated. The results demonstrated that the BBR and GA combination exhibited significant antiviral and cytoprotective activities against CAPRV2023 in a time-dependent manner. The combined administration significantly enhanced the survival rate of CAPRV2023-infected Trachinotus anak, reaching up to 63.33%, while concurrently reducing tissue viral loads markedly. This comprehensive protective effect of the combination therapy is primarily attributed to its dual regulatory mechanisms of suppressing viral replication and alleviating host tissue damage. Specifically, this is achieved by attenuating NF-κB-mediated inflammatory cascade amplification, modulating apoptosis-related stress, and regulating immune and oxidative factors including IFN1, RIG-I, Mx, IL-1β, TNF-α, Caspase-3, SOD, and MDA. Overall, these findings indicate that the BBR and GA combination may represent a promising candidate strategy for CAPRV2023 prevention and control, pending further validation, providing preliminary experimental evidence for developing candidate antiviral intervention strategies in marine aquaculture.
Weicong Li, Heng Sun, Haoyu Wang et al.· Fish and Shellfish Immunolog...· 0 citations
The present review offered an updated theoretical basis for understanding the structure-activity relationship of HKL and provided insights into its translation from bench to bedside and critically evaluated recently developed strategies to overcome its pharmacokinetic limitations.
It is demonstrated that diarylheptanoids are the major anti-inflammatory components in A. maximum fruits, which not only validates the ethnopharmacological use of this herb, but also provides new anti-inflammatory agents derived from natural products.
Tripterygium wilfordii, a traditional Chinese botanical drug, has emerged as a rich source of bioactive metabolites with promising therapeutic potential. Among its metabolites, diterpenoids and triterpenoids—such as triptolide, triptonide, and celastrol—exhibit potent immunosuppressive, anti-inflammatory, and anti-tumor properties through modulation of key molecular pathways including NF-κB, JAK/STAT, and TGF-β/Smad. This review provides a comprehensive overview of the chemical classification, pharmacological mechanisms, and clinical translation of major metabolites derived from T. wilfordii. It highlights their application in autoimmune diseases, cancer, fibrosis, and metabolic disorders, while addressing current challenges in safety, solubility, and bioavailability. Advancements in drug delivery systems, structural modification, and precision medicine approaches are also discussed. Together, these insights aim to guide future research and translational development of T. wilfordii-based compoundic therapeutics.
Yujie Jin, Jiahao Xu, Xiangyu Yan et al.· Frontiers in Pharmacology· 0 citations
