Table 1.
Antiviral activity of glycyrrhizin (glycyrrhizic acid) and boswellic acids against SARS-CoV-2 and mechanism of action in articles published through July 2022
| Active ingredient | Method of research | Major finding | Mechanism of actions | References |
|---|---|---|---|---|
| Glycyrrhizic acid (GB-1) |
Cell culture ACE2/SARS-CoV-2 spike inhibitor screening assay |
Glycyrrhizic acid showed prophylaxis action against different variants of SARS-CoV-2 infection | Glycyrrhizic acid inhibits binding between ACE2 and RBD with different mutations | Tsai et al. (2022) |
| Glycyrrhizinic acid (Glyc) and its derivative (acylation with nicotinic acid) | Antiviral activity against three strains of SARS-CoV-2 was tested in vitro on Vero E6 cells and MTT assay | They have low toxicity and a broad spectrum of antiviral action against three strains of SARS-CoV-2 and HIV pseudovirus infection | Interfered with virus entry into the target cell | Fomenko et al. (2022) |
| The triterpenoids licorice-saponin A3 (A3) and glycyrrhetinic acid | Experimental in vitro experiments in vivo and autodocking | GA and A3 from licorice potently inhibit SARS-CoV-2 infection by affecting entry and replication of the virus | By targeting nsp7 and the spike protein RBD, | Yi et al. (2021) |
| Glycyrrhizin | In vitro, cellular perturbations in lung cells, macrophages cultured in conditioned media from lung cells | Glycyrrhizin inhibited SARS-CoV-2 replication in Vero E6 cells without exhibiting cytotoxicity at high doses. Glycyrrhizin mitigated viral proteins induced lung cell pyroptosis and activation of macrophages and resolving hyper-inflammatory processes | Glycyrrhizin prevents SARS-CoV-2 S1 and Orf3a induced high mobility group box 1 (HMGB1) release and inhibits viral replication | Gowda et al. (2021)*** |
| Glycyrrhizic acid (GA) nanoparticles (GANPs) | In vitro and in vivo studies in mouse model of COVID-19 | GANPs and GA exert antiviral and anti-inflammatory effects, relieving organ damage and conferring a significant survival advantage to infected mice | GANPs and GA could prominently suppress the proliferation of COVID-19 | Zhao et al. (2021a, b) |
| Licorice extract and glycyrrhizin | Computational and in vitro experimental investigations | In vitro studies demonstrated robust anti-SARS-CoV-2 activity of licorice and glycyrrhizin under different treatment protocols (simulations treatment with viral infection, post-infection treatment, and pre-treatment, | Multiple mechanisms for action. Inhibitors for SARS-CoV-2 main protease (Mpro) | Tolah et al. (2021) |
| Glycyrrhizic acid | Experimental in vitro and Docking analysis | Glycyrrhizic acid inhibits SARS-CoV-2 infection | By blocking spike protein-mediated cell attachment. Molecules | Li et al. (2021) |
|
Glycyrrhizic acid Comparing with ginsenoside Ra2, ginsenoside Rb3, berberine chloride |
Combination of computer-aided drug design and in vitro biological verification | Glycyrrhizic acid was found to be the most efficient and nontoxic broad-spectrum anti-coronavirus molecule in vitro, especially, the significant effect on SARS-CoV-2 | Glycyrrhizic acid performed the best in disrupting the interaction between the RBD of SARS-CoV-2 and ACE2 | Yu et al. (2021) |
| Glycyrrhiza glabra extract contains 6.25% of glycyrrhizinic acid | Rats in normal or stress condition | This study provide evidence that glycyrrhiza glabra extract may reduce an entry point of SARS-CoV-2 | Glycyrrhiza glabra root extract leads to a significant reduction in the expression of ACE2 in the small intestine | Jezova et al. (2021) |
| Glycyrrhizin | In vitro, Vero E6 cells | Glycyrrhizin potently blocks SARS-CoV-2 replication | Protease inhibitory activity of glycyrrhizin on the SARS-CoV-2 main protease Mpro | van de Sand et al (2021) |
| Ephedra and glycyrrhiza | Molecular docking | Ephedra and glycyrrhiza have antiviral activity against COVID-19 through multiple targets and pathways | The active compounds from the Ephedra-Glycyrrhiza pair bound well to COVID-19-related targets, including the main protease (Mpro, also called 3CLpro), the spike protein (S protein), and the angiotensin-converting enzyme 2 (ACE2) | Li et al. (2021) |
| Licorice and glycyrrhizic acids | Molecular docking, Autodock vina software | Glycyrrhizic acid could be considered as the best molecule from licorice, which could find useful activity against SARS-CoV-2 | Glycyrrhizic acid was found to be best suited for the binding pocket of spike glycoprotein and inhibited the entry of the virus into the host cell | Sinha et al. (2021) |
| Glycyrrhizin | Blind docking approach, AutoDock | Glycyrrhizin is inhibitors against ACE2 host receptor binding of SARS-CoV-2 | Glycyrrhizin show strong binding with ACE2. These compounds bind at the H1-H2 binding pocket | Ahmad et al. (2021) |
| Natural antioxidants including glycyrrhizin and its metabolite 18-glycyrrhetinic acid | Molecular docking, and MD simulations | Glycyrrhizin was found as the best ligand showing strong inhibition of five SARS-CoV-2 proteins | Glycyrrhizin and its metabolite 18-glycyrrhetinic acid have shown a strong binding affinity for MPro, helicase, RdRp, spike, and E-channel proteins, while a flavonoid Baicalin also strongly binds against PLpro and RdRp | Rehman et al. (2021) |
| 56 licorice compounds | Silico interaction of main licorice components against SARS-CoV-2 infection | Glycyrrhizic acid, considered as a licorice major active ingredient, have a significant antiviral effects | Glycyrrhizic acid have the highest affinity to all targets | Maddah et al. (2021) |
| β-Boswellic acid and glycyrrhizic acid comparing with many compounds | Molecular docking studies to identify binding of medicinal metabolites with SARS-CoV-2 E protein | Out of screened compounds, β-boswellic acid (B. serrata) was found to be most suitable, along with glycyrrhizic acid (G. glabra) antiviral activities against enveloped viruses | They are strong SARS-CoV-2 E protein inhibitors | Fatima et al. (2022) |
| Bioactive compounds from Boswellia serrata | Computational method. AutoDock and PATCHDOCK | It was found that Euphane possesses most significant inhibitory potential against all of four receptors of virus | The top five ligands, bioactive compounds, bind to the catalytic dyad amino acid residues of Mpro by different bonding interactions | Roy and Menon (2022) |
| Acetyl‐11‐keto‐β‐boswellic acid (AKBA), 11‐keto‐β‐boswellic acid (KBA), and β‐boswellic acid (BBA) | Molecular modeling and bioinformatics | BAs have been reported to possess antiviral properties as antiviral drugs | The data of this bioinformatics study suggest that BAs target SARS‐CoV‐2 viruses on an atomic scale on three functional proteins, which in turn are responsible for human cell adhesion or viral RNA replication | Caliebe et al. (2021) |
| Alpha-boswellic acid (ABA) and beta-boswellic acid (BBA) which are active components | Docking studies |
The binding of the ABA and BBA with the spike of the virus could inhibit its reproduction The LC50 values indicated that a high amount of ABA and BBA could be used safely in the human body |
Binding energy indicates the high affinity between the spike proteins with the studied compounds | Kadhim et al. (2021) |