Ayurveda botanicals in COVID-19 management: An in silico multi-target approach

PLoS One. 2021 Jun 11;16(6):e0248479. doi: 10.1371/journal.pone.0248479. eCollection 2021.

Abstract

The Coronavirus disease (COVID-19) caused by the virus SARS-CoV-2 has become a global pandemic in a very short time span. Currently, there is no specific treatment or vaccine to counter this highly contagious disease. There is an urgent need to find a specific cure for the disease and global efforts are directed at developing SARS-CoV-2 specific antivirals and immunomodulators. Ayurvedic Rasayana therapy has been traditionally used in India for its immunomodulatory and adaptogenic effects, and more recently has been included as therapeutic adjuvant for several maladies. Amongst several others, Withania somnifera (Ashwagandha), Tinospora cordifolia (Guduchi) and Asparagus racemosus (Shatavari) play an important role in Rasayana therapy. The objective of this study was to explore the immunomodulatory and anti SARS-CoV2 potential of phytoconstituents from Ashwagandha, Guduchi and Shatavari using network pharmacology and docking. The plant extracts were prepared as per ayurvedic procedures and a total of 31 phytoconstituents were identified using UHPLC-PDA and mass spectrometry studies. To assess the immunomodulatory potential of these phytoconstituents an in-silico network pharmacology model was constructed. The model predicts that the phytoconstituents possess the potential to modulate several targets in immune pathways potentially providing a protective role. To explore if these phytoconstituents also possess antiviral activity, docking was performed with the Spike protein, Main Protease and RNA dependent RNA polymerase of the virus. Interestingly, several phytoconstituents are predicted to possess good affinity for the three targets, suggesting their application for the termination of viral life cycle. Further, predictive tools indicate that there would not be adverse herb-drug pharmacokinetic-pharmacodynamic interactions with concomitantly administered drug therapy. We thus make a compelling case to evaluate the potential of these Rasayana botanicals as therapeutic adjuvants in the management of COVID-19 following rigorous experimental validation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / metabolism*
  • Antiviral Agents / pharmacokinetics
  • Asparagus Plant / chemistry*
  • Binding Sites
  • COVID-19 / metabolism*
  • COVID-19 / virology
  • COVID-19 Drug Treatment
  • Coronavirus 3C Proteases / metabolism
  • Coronavirus RNA-Dependent RNA Polymerase / metabolism
  • Herb-Drug Interactions
  • Humans
  • Immunologic Factors / metabolism*
  • Immunologic Factors / pharmacokinetics
  • India
  • Medicine, Ayurvedic / methods
  • Molecular Docking Simulation / methods*
  • Phytotherapy / methods
  • Plant Extracts / metabolism*
  • Plant Extracts / pharmacokinetics
  • Protein Binding
  • SARS-CoV-2 / enzymology*
  • Spike Glycoprotein, Coronavirus / metabolism
  • Tinospora / chemistry*
  • Withania / chemistry*

Substances

  • Antiviral Agents
  • Immunologic Factors
  • Plant Extracts
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Coronavirus RNA-Dependent RNA Polymerase
  • Coronavirus 3C Proteases
  • Ashwagandha

Grants and funding

The work was funded by the Ministry of AYUSH, Govt. of India (Grant no. Z 15015/07/2017-COE; Dt. 27/11/2017). The funder provided support in the form of salaries/fellowship for authors [SB, AS, VB], but did not have any additional role in the study design, data collection, and analysis, decision to publish, or preparation of the manuscript. Pharmanza Herbals Pvt. Ltd provided support in the form of salaries for authors [AG, LH] and supplied the herbal extracts as a gift, but did not have any additional role in the study design, data collection, and analysis, decision to publish, or preparation of the manuscript. The specific roles of authors are provided in the author contributions section.