Withanolides from <i>Withania somnifera</i> as an immunity booster and their therapeutic options against COVID-19
Creators: name: Khanal, Pukar
name: Chikhale, Rupesh
name: Dey, Yadu Nandan
name: Pasha, Ismail
name: Chand, Sharad
name: Gurav, Nilambari
name: Ayyanar, Muniappan
name: Patil, B. M.
name: Gurav, Shailendra
Publisher: name: Taylor & Francis
Year: 2021
Subjects: subject: Biophysics
subject: Biochemistry
subject: Genetics
subject: FOS: Biological sciences
subject: Pharmacology
subject: Evolutionary Biology
subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences
subject: Immunology
subject: FOS: Clinical medicine
subject: 69999 Biological Sciences not elsewhere classified
subject: 110309 Infectious Diseases
subject: FOS: Health sciences
subject: 60506 Virology

description: Traditionally, <i>Withania somnifera</i> is widely used as an immune booster, anti-viral, and for multiple medicinal purposes. The present study investigated the withanolides as an immune booster and anti-viral agents against the coronavirus-19. Withanolides from <i>Withania somnifera</i> were retrieved from the open-source database, their targets were predicted using DIGEP-Pred, and the protein-protein interaction was evaluated. The drug-likeness score and intestinal absorptivity of each compound were also predicted. The network of compounds, proteins, and modulated pathways was constructed using Cytoscape, and docking was performed using autodock4.0, and selected protein-ligand complexes were subjected to 100 ns Molecular Dynamics simulations. The molecular dynamics trajectories were subjected to free energy calculation by the MM-GBSA method. Withanolide_Q was predicted to modulate the highest number of proteins, showed human intestinal absorption, and was predicted for the highest drug-likeness score. Similarly, combined network interaction identified Withanolide_Q to target the highest number of proteins; RAC1 was majorly targeted, and fluid shear stress and atherosclerosis associated pathway were chiefly regulated. Similarly, Withanolide_D and Withanolide_G were predicted to have a better binding affinity with PLpro, Withanolide_M with 3CLpro, and Withanolide_M with spike protein based on binding energy and number of hydrogen bond interactions. MD studies suggested Withanoside_I with the highest binding free energy (ΔG<sub>bind</sub>-31.56 kcal/mol) as the most promising inhibitor. Among multiple withanolides from <i>W. somnifera,</i> Withanolide_D, Withanolide_G, Withanolide_M, and Withanolide_Q were predicted as the lead hits based on drug-likeness score, modulated proteins, and docking score to boost the immune system and inhibit the COVID-19 infection, which could primarily act against COVID-19. HighlightsWithanolides are immunity boosters.Withanolides are a group of bio-actives with potential anti-viral properties.Withanolide_G, Withanolide_I, and Withanolide_M from <i>Withania somnifera</i> showed the highest binding affinity with PLpro, 3CLpro, and spike protein, respectively.Withanolides from <i>Withania somnifera</i> holds promising anti-viral efficacy against COVID-19. Withanolides are immunity boosters. Withanolides are a group of bio-actives with potential anti-viral properties. Withanolide_G, Withanolide_I, and Withanolide_M from <i>Withania somnifera</i> showed the highest binding affinity with PLpro, 3CLpro, and spike protein, respectively. Withanolides from <i>Withania somnifera</i> holds promising anti-viral efficacy against COVID-19. Communicated by Vsevolod Makeev