Withaferin A for COVID-19: a Network Pharmacology Approach

Abstract

COVID-19 has become a global challenge as there are very few treatment options available. This has proved to impact several physiological implications like immunological injury, myocardial infarction, micro-thrombus formation, neurological complications and multi-organ dysfunction. A combination therapy or a systems pharmacology approach can be adopted to fight against COVID-19. Here, we have proposed withaferin A as a system pharmacophore employing molecular docking strategy using AutoDock Vina and utilising different bioinformatics tools like PharmMapper, STRING database and PANTHER Pathway enrichment analysis. Docking results show that withaferin A exhibits a significant binding affinity with P2Y12 receptor, vitamin D-binding protein and annexin A5, hence implying that it could play a role in anti-thrombosis. Protein-protein interaction network showed its importance in innate immune system. Results also show that this molecule may have significant potential to modulate T cell activation too. Text mining results showed association of STAT3 with withaferin A. Our studies propose that withaferin A might also conquer the cytokine storm via STAT3. This study concludes that two strong targets of withaferin A, i.e. vitamin D-binding protein and STAT3, have been identified and that withaferin A can be used as a system pharmacophore for drug development in order to combat COVID-associated complicacies.

Keywords: Antithrombotic; COVID-19; Immunomodulation; Neuro-inflammation; Withaferin A.

Fig. 1

The 2D interaction diagram of withaferin with targets by Discovery Studio. The targets are as follows: a P2Y12 co-crystalised molecule, interaction energy =  − 10.1 kcal/mol. b P2Y12 withaferin A, interaction energy =  − 6.7 kcal/mol. c P2Y1 co-crystalised molecule, MRS; interaction energy =  − 8.6 kcal/mol. d P2Y1, withaferin A, interaction energy =  − 9.5 kcal/mol

Fig. 2

The 2D interaction diagram of withaferin A with 7 targets by Discovery Studio. The targets are as follows: a protein interleukin 1, beta convertase. b Migration inhibitory factor protein S100-A9. c Histamine N-methyltransferase. d Leukocyte (neutrophil) elastase. e Vitamin D-binding protein. f Annexin A5. g Alpha1-Antitrypsin

Fig. 3

Red: cancer pathway. Blue: immune system. Green: innate immune system

Fig. 4

PANTHER Pathway enrichment analysis for pathways affected by withaferin A

Fig. 5

Text mining of the literature on withaferin A