Identification of bioactive compounds fromGlycyrrhiza glabraas possible inhibitor of SARS-CoV-2 spike glycoprotein and non-structural protein-15: a pharmacoinformatics study

Abstract

Aim: In view of the strong immunomodulatory and antiviral activity of andrographolide and its derivative, the present study aimed to investigate the binding a nities of andrographolide and its derivative 14deoxy-11,12-didehydroandrographolide with 3 major targets of COVID-19 i.e. 3CLpro, PLpro and spike protein followed by their gene-set enrichment analysis with special reference to immune modulation. Materials and methods: SMILES of the compounds were retrieved from DigepPred database and the proteins identi ed were queried in STRING to evaluate the protein-protein interaction and modulated pathways were identi ed concerning the KEGG database. Drug-likeness and ADMET pro les were evaluated using MolSoft and admet SAR 2.0, respectively. Molecular docking was carried using autodock 4.0. Results: Andrographolide and 14-Deoxy-11,12-didehydroandrographolide were predicted to have a high binding a nity with papain-like protease i.e.-6.7 kcal/mol and-6.5 kcal/mol, respectively while they interact with equal binding energies with 3clpro (-6.8 kcal/mol) and spike protein (-6.9 kcal/mol). Network pharmacology analysis revealed that both compounds modulated the immune system through the regulation of chemokine signaling pathway, Rap1 signaling pathway, Cytokine-cytokine receptor interaction, MAPK signaling pathway, NF-kappa B signaling pathway, Rassignaling pathway, p53 signaling pathway, HIF-1 signaling pathway, and Natural killer cell-mediated cytotoxicity. Although the 14deoxy-11,12-didehydroandrographolide scored higher drug-likeness character, it showed less potency to interaction with targeted proteins of COVID-19. Conclusion: The study suggests the strong interaction of the andrographolide and its derivative 14-deoxy-11,12-didehydroandrographolide against target proteins associated with COVID-19. Further, network pharmacology analysis elucidated the different pathways of immunomodulation. However, clinical research should be conducted to con rm the current ndings.

“Fei Yan No. 1” as a Combined Treatment for COVID-19: An Efficacy and Potential Mechanistic Study

“…From binding energy and interaction studies, Saikosaponins U and V displayed the strongest affinity towards the S protein ( Sinha et al, 2020a ). Similarly, a molecular docking simulation study of 20 compounds and an additional simulation study using molecular dynamics (MD) found that components of glycyrrhizic acid and glyasperin A displayed high binding affinity towards the S protein ( Sinha et al, 2020b ). COVID-19 principally spreads through the respiratory tract, and so the pharynx is a location that the virus can be found in high concentration.…”

The role of kallikrein-kinin and renin-angiotensin systems in COVID-19 infection

“…ORF1a/b located at the 5′ end encodes 16 non-structural proteins (NSPs) called NSP1 to NSP16. In addition, other ORFs at the 3′ end encode accessory and structural proteins [ [16] , [17] , [18] ], including spike (S) protein responsible for anchoring the virus to the receptor and subsequent fusion of the membrane, thereby mediating the entry of the virus into the cell; the envelope protein (E) plays a pivotal role in the assembly and release of the virus in addition to exercising the ion channel function necessary for the pathogenesis of SARS-CoV-2. The membrane protein (M) assists in maintenance of the membrane curvature and binding to the nucleocapsid whereas the nucleocapsid protein (N) is involved in the packaging of the viral genome encapsulated in the viral particles and its interaction with the M and NSP3 proteins [ 19 ].…”

Natural products from the traditional Moroccan pharmacopoeia: A potential lead for the prevention and treatment of COVID-19

“…Glycyrrhizin was found more active than ribavirin, 6-aziridine, pyrazofurin and the Mycophenolic acid (Cinatl et al, 2003). Another study aimed at identifying in-silico the activity of molecules derived from licorice against two targets of SARS-CoV-2, the Spike protein and the endoribonuclease Nsp 15, has shown, via the analysis of molecular docking and molecular dynamics, that Glycyrrhizic Acid has a high af inity which can inhibit the Spike protein of SARS-CoV-2 (Sinha et al, 2020).…”