Network pharmacology of AYUSH recommended immune-boosting medicinal plants against COVID-19

Chikhale

Informatics in Medicine Unlocked

et al. 2021

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Bioflavonoids are the largest group of plant-derived polyphenolic compounds with diverse biological potential and have also been proven efficacious in the treatment of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The present investigation validates molecular docking, simulation, and MM-PBSA studies of fifteen bioactive bioflavonoids derived from plants as a plausible potential antiviral in the treatment of COVID-19. Molecular docking studies for 15 flavonoids on the three SARS CoV-2 proteins, non-structural protein-15 Endoribonuclease (NSP15), the receptor-binding domain of spike protein (RBD of S protein), and main protease (M pro /3CL pro ) were performed and selected protein-ligand complexes were subjected to Molecular Dynamics simulations. The molecular dynamics trajectories were subjected to free energy calculation by the MM-PBSA method. All flavonoids were further assessed for their effectiveness as adjuvant therapy by network pharmacology analysis on the target proteins. The network pharmacology analysis suggests the involvement of selected bioflavonoids in the modulation of multiple signaling pathways like p53, FoxO, MAPK, Wnt, Rap1, TNF, adipocytokine, and leukocyte transendothelial migration which plays a significant role in immunomodulation, minimizing the oxidative stress and inflammation. Molecular docking and molecular dynamics simulation studies illustrated the potential of glycyrrhizic acid, amentoflavone, and mulberroside in inhibiting key SARS-CoV-2 proteins and these results could be exploited further in designing future ligands from natural sources.

Section: Resultsmentioning

confidence: 99%

Computational and network pharmacology analysis of bioflavonoids as possible natural antiviral compounds in COVID-19

Chikhale

Informatics in Medicine Unlocked

et al. 2021

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“…Three targets of novel coronavirus i.e. 3C-like protease (3CLpro), papain-like protease (PLpro), and spike protein [3][4][5][6] are being targeted by multiple investigators to identify the new hit molecule for the management of COVID-19. Further, inflammation and cell necrosis are contributing factors in worsening the COVID-19 pathogenesis which suggests identifying the molecule with anti-viral, anti-inflammatory and immune-boosting properties.…”

Section: Introductionmentioning

confidence: 99%

Anthraquinone Derivatives as an Immune Booster and their Therapeutic Option Against COVID-19

Nat. Prod. Bioprospect.

Chand

et al. 2020

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Anthraquinone derivatives are identified for their immune-boosting, anti-inflammatory, and anti-viral efficacy. Hence, the present study aimed to investigate the reported anthraquinone derivatives as immune booster molecules in COVID-19 infection and evaluate their binding affinity with three reported targets of novel coronavirus i.e. 3C-like protease, papain-like protease, and spike protein. The reported anthraquinone derivatives were retrieved from an open-source database and filtered based on a positive druglikeness score. Compounds with positive druglikeness scores were predicted for their targets using DIGEP-Pred and the interaction among modulated proteins was evaluated using STRING. Further, the associated pathways were recorded concerning the Kyoto Encyclopedia of Genes and Genomes pathway database. Finally, the docking was performed using autodock4 to identify the binding efficacy of anthraquinone derivatives with 3C-like protease, papain-like protease, and spike protein. After docking the pose of ligand scoring minimum binding energy was chosen to visualize the ligand–protein interaction. Among 101 bioactives, 36 scored positive druglikeness score and regulated multiple pathways concerned with immune modulation and (non-) infectious diseases. Similarly, docking study revealed torososide B to possess the highest binding affinity with papain-like protease and 3C-like protease and 1,3,6-trihydroxy-2-methyl-9,10-anthraquinone-3-O-(6′-O-acetyl)-β-d-xylopyranosyl-(1 → 2)-β-d-glucopyranoside with spike protein. Graphic Abstract

“…Hence, it is important to identify any alternative approach as prophylaxis against COVID-19 which can be implemented via the utilization of immune boosters from natural sources. Three targets 3C-like protease (3CLpro), papain-like protease (PLpro), and spike protein [3][4][5][6] are being targeted by multiple investigators to identify the new hit molecule for the management of COVID-19. Further, in COVID-19 infection severe in ammation and cell necrosis are contributing to the worsening of pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

Anthraquinone derivatives as an immune booster and their therapeutic option against COVID-19

Chand

et al. 2020

Preprint

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Multiple Anthraquinolines derivatives are reported for their immune-boosting, anti-inflammatory and anti-viral efficacy. Hence, the present study dealt to investigate the reported anthraquinone derivatives as an immune booster molecule in COVID-19 infection and evaluate their binding affinity with three reported targets of novel coronavirus i.e. 3CLpro, PLpro and spike proteins. The reported anthraquinone derivatives were retrieved from an open-source database and filtered based on a positive druglikeness score. Further, the probably modulated gene by compounds with positive druglikeness score was evaluated for the modulation of proteins using DIGEP-Pred and the interaction of proteins was evaluated using STRING; associated pathways were recorded concerning the KEGG pathway database. Finally, docking was carried using autodock4; pose scoring minimum binding energy was chosen to visualize the ligand-protein interaction. Among 101 compounds, 36 scored positive druglikeness scores; modulating multiple pathways for immune-boosting as well as pathways involved in infectious and non-infectious diseases. Similarly, docking study revealed torososide B to have the highest binding affinity with PLpro and 3clpro and 1,3,6-trihydroxy-2-methyl-9,10-anthraquinone-3-O-(6'-O-acetyl)-β-D-xylopyranosyl-(1->2)-β-D-glucopyranoside with spike protein