Prophylactic and therapeutic potential of selected immunomodulatory agents from Ayurveda against coronaviruses amidst the current formidable scenario: an in silico analysis

Abstract

There is currently a dearth of specific therapies to treat respiratory infections caused by the three related species of coronaviruses viz. SARS-CoV-2, SARS-CoV and MERS-CoV. Prevention from disease is currently the safest and most convenient alternative available. The present study aimed to evaluate the preventive and therapeutic effect of fifteen phytoconstituents from medicinal plants of Ayurveda against coronaviruses by in silico screening. All the phytoconstituents exhibited rapid GI absorption and bioavailability and most of them had no toxicity versus reference drug chloroquine. BAS analyses revealed that most of the phytocomponents had favorable bioactivity scores towards biological target proteins. Principal component analysis revealed that most of the phytoconstituents fell close to chloroquine in 3D projection of chemical space. Affinity of phytoconstituents towards SARS-CoV-2 spike protein-human ACE2 complex decreased as isomeldenin > tinosporaside > EGCG whereas in case of unbound ACE2, the strength of binding followed the order isomeldenin > tinosporaside > ellagic acid. Towards SARS-CoV-2 main and papain-like proteases, the affinity decreased as isomeldenin > EGCG > tinosporaside and EGCG > tinosporaside > isomeldenin, respectively. Most phytoconstituents displayed significant binding kinetics to the selected protein targets than chloroquine. SAR analysis revealed that isomeldenin, tinosporaside, EGCG and ellagic acid bind to viral spike glycoproteins via H-bond, Pi-Pi, Pi-sigma and Pi-alkyl type interactions. Molecular dynamics simulation of isomeldenin and EGCG with SARS-CoV and SARS-CoV-2 spike glycoproteins exhibited low deviations throughout the 100 ns simulation indicating good stability and compactness of the protein-ligand complexes. Thus, the above four phytoconstituents have the potential to emerge as prophylactic and therapeutic agents against coronaviruses if investigated further in vitro and in vivo.

Graphical Abstract

Communicated by Ramaswamy H. Sarma

Keywords:

• Immunoboosting agents
• spike glycoprotein
• ACE2
• coronaviruses
• Ayurveda
• COVID-19

Acknowledgements

The authors gratefully acknowledge Dr. Meraj Ahmad, Professor, Dept. of Sociology, University of Lucknow, Lucknow, India, for being the inspiration and motivation behind the present work in view of his exceptional work and contribution in the area of social sciences, social work, humanities and public health. The present study did not receive any extramural or intramural grant from funding agencies in the public, commercial, or not-for-profit sectors.

Disclosure statement

The authors declare that they have no competing interests.

Author contributions

RA planned, conceptualized and supervised the study as well as drafted, edited and revised the manuscript. AT, SS, AS, AG, SU, IH and RA carried out the computational analyses viz. molecular docking, molecular chemoinformatics, molecular dynamics simulation using LARMD online server, calculations, data analysis and interpretation whereas TA and MFK carried out molecular dynamics simulation studies using Schrödinger Release 2020-4 package. SS, MAK, SM, AM, ZS, GA, and SK co-supervised the study, provided critical inputs as well as co-edited, revised and critically reviewed the manuscript whereas BA co-ordinated the overall study design. All authors read and approved the final manuscript.