Glycyrrhizin as a promising kryptonite against SARS-CoV-2: Clinical, experimental, and theoretical evidences

Abstract

COVID-19 is the most devastating disease in recent times affecting most people globally. The higher rate of transmissibility and mutations of SARS-CoV-2 along with the lack of potential therapeutics has made it a global crisis. Potential molecules from natural sources could be a fruitful remedy to combat COVID-19. This systematic review highlights the detailed therapeutic implication of naturally occurring glycyrrhizin and its related derivatives against COVID-19. Glycyrrhizin has already been established for blocking different biomolecular targets related to the SARS-CoV-2 replication cycle. In this article, several experimental and theoretical evidences of glycyrrhizin and related derivatives have been discussed in detail to evaluate their potential as a promising therapeutic strategy against COVID-19. Moreover, the implication of glycyrrhizin in traditional Chinese medicines for alleviating the symptoms of COVID-19 has been reviewed. The potential role of glycyrrhizin and related compounds in affecting various stages of the SARS-CoV-2 life cycle has also been discussed in detail. Derivatization of glycyrrhizin for designing potential lead compounds along with combination therapy with other anti-SARS-CoV-2 agents followed by extensive evaluation may assist in the formulation of novel anti-coronaviral therapy for better treatment to combat COVID-19.

Keywords: 11β-HSD, 11β-hydroxysteroid dehydrogenase; 3CLpro, 3-chymotrypsin-like protease; ACE2, Angiotensin converting enzyme 2; ADMET, absorption distribution metabolism excretion and toxicity; ARDS, acute respiratory distress syndrome; CHM, Chinese herbal medicine; CNS, central nervous system; COVID-19, Coronavirus Disease 2019; CTD, C-terminal domain; Experimental and computational evidences; Glycyrrhizin; HMGB1, high-mobility-group box1; IL, Interleukin; INF-γ, interferon-γ; KEGG, Kyoto Encyclopedia of Genes and Genomes; MD, molecular dynamics; MERS, Middle East respiratory syndrome; MM/GBSA, Molecular Mechanics/Generalized Born Surface Area; MM/PBSA, Molecular Mechanics Poisson-Boltzmann Surface Area; MR, mineralocorticoid receptor; Molecular docking interactions; NO, nitric oxide; NTD, N-terminal domain; ORF, open reading frame; PLpro, papain-like protease; RBD, receptor-binding domain; RMSD, Root mean square deviation; RMSF, Root mean square fluctuation; ROS, reactive oxygen species; RSV, respiratory syncytial virus; RTC, replication-transcription complex; RdRp, RNA-dependent RNA polymerase; SARS-CoV-2; SARS-CoV-2, Severe acute respiratory syndrome coronavirus-2; SI, Selectivity index; TCM, Traditional Chinese Medicine; TLR, Toll-like receptor; TNF-α, Tumor necrosis factor α; Traditional Chinese medicine; nsp, non-structural protein.