Preprint / Version 1

Pharmacoinformatic approach to identify potential phytochemicals against SARS-CoV-2 spike receptor-binding domain in native and variants of concern

Authors

  • Raj Chinnadurai Mahatma Gandhi Medical Advanced Research Institute, Sri Balaji Vidhyapeeth (Deemed to be University), Pondicherry, 607402 India
  • Saravanaraman Ponne Department of Biotechnology, Pondicherry University, Pondicherry, 605014 India
  • Loganathan Chitra Department of Biochemistry, Periyar University, Salem, Tamil Nadu 636011 India
  • Rajender Kumar Division of Glycoscience, Department of Chemistry, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, AlbaNova University Center, 106 91 Stockholm, Sweden
  • Palvannan Thayumanavan Department of Biochemistry, Periyar University, Salem, Tamil Nadu 636011 India
  • Balanehru Subramanian School of Biological Sciences, Sri Balaji Vidhyapeeth (Deemed to be University), Pondicherry, 607402 India

Keywords:

SARS-CoV-2, COVID-19, Phytochemicals, Receptor-binding domain, Virtual screening, Molecular dynamics

Abstract

Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) pathogenesis is initiated by the binding of SARS-CoV-2 spike (S) protein with the angiotensin-converting enzyme 2 receptor (ACE2R) on the host cell surface. The receptor-binding domain (RBD) of the S protein mediates the binding and is more prone to mutations resulting in the generation of different variants. Recently, molecules with the potential to inhibit the interaction of S protein with ACE2R have been of interest due to their therapeutic value. In this context, the present work was performed to identify potential RBD binders from the Indian medicinal plant's phytochemical database through virtual screening, molecular docking, and molecular dynamic simulation. Briefly, 1578 compounds filtered from 9596 phytochemicals were chosen for screening against the RBD of the native SARS-CoV-2 S protein. Based on the binding energy, the top 30 compounds were selected and re-docked individually against the native and five variants of concern (VOCs: alpha, beta, gamma, delta, and omicron) of SARS-CoV-2. Four phytochemicals, namely withanolide F, serotobenine, orobanchol, and gibberellin A51, were found to be potential RBD binders in native and all SARS-CoV-2 VOCs. Among the four, withanolide F exhibited lower binding energy (− 10.84 to − 8.56 kcal/mol) and better ligand efficiency (− 0.3 to − 0.25) against all forms of RBD and hence was subjected to a 100 ns MD simulation which confirmed its stringent binding to the RBDs in native and VOCs. The study prioritizes withanolide F as a prospective COVID-19 (Coronavirus disease) therapeutic agent based on the observations. It warrants deeper investigations into the four promising leads for understanding their precise therapeutic value. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s11030-022-10580-9. Keywords: SARS-CoV-2, COVID-19, Phytochemicals, Receptor-binding domain, Virtual screening, Molecular dynamics