The role of andrographolide and its derivative in COVID-19 associated proteins and immune system
Yadu Nandan Dey, Pukar Khanal, B M Patil, Manish M Wanjari, Bhavana Srivast, Shailendra S Gurav, Sudesh N Gaidhani
doi:10.21203/rs.3.rs-35800/v1
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.
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'abstract': '<jats:title>Abstract</jats:title>\n'
' <jats:p><jats:bold>Aim: </jats:bold>In view of the strong immunomodulatory and '
'antiviral activity of andrographolide and its derivative, the present study aimed to '
'investigate the binding affinities of andrographolide and its derivative '
'14-deoxy-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.<jats:bold>Materials and methods:</jats:bold> SMILES of the compounds were '
'retrieved from DigepPred database and the proteins identified were queried in STRING to '
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'</jats:bold>Andrographolide and 14-Deoxy-11,12-didehydroandrographolide were predicted to '
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'modulated the immune system through the regulation of chemokine signaling pathway, Rap1 '
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'potency to interaction with targeted proteins of COVID-19.<jats:bold>Conclusion: '
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