Identification of phytocompounds as newer antiviral drugs against COVID-19 through molecular docking and simulation based study

https://doi.org/10.1016/j.jmgm.2022.108192Get rights and content

Highlights

  • Dual targeting phytocompounds against COVID-19 proteins (Mpro and Spike).

  • Oleanderolide, Balsaminone A, Proceragenin A were docked against the target proteins.

  • ADMET properties were screened to check pharmacokinetic activity.

  • MD simulation study revealed oleanderolide performed better than the rest two.

Abstract

COVID-19 pandemic has emerged as a global threat with its highly contagious and mutating nature. Several existing antiviral drugs has been worked on, without proper results and meanwhile the virus is mutating rapidly to create more infectious variant. In order to find some alternatives, phytocompounds can be opted as good one. In this study, three hundred phytocompounds were screened virtually against two viral proteins namely main protease and spike protein. Molecular docking and dynamic simulation study was used to find binding affinity, structural stability and flexibility of the complex. Pharmacokinetic properties were studied through ADMET analysis. To understand energy variation of the complex structure free energy landscape analysis was performed. Among three hundred phytocompounds virtual screening, three phytocompounds were selected for detailed molecular interaction analysis. Oleanderolide, Proceragenin A and Balsaminone A, showed strong binding affinity against both the target proteins and reflected conformational stability throughout the MD run. Oleanderolide, proceragenin A and balsaminone A has docking score −9.4 kcal/mol, −8.6 kcal/mol, and −8.1 kcal/mol respectively against main protease and same −8.3 kcal/mol docking score against spike protein. These three phytocompounds has high gastrointestinal absorption capacity. They were unexplored till now for their antiviral activity. Their promising in silico results suggests that they can be promoted in the long run for development of new antiviral drugs.

Graphical abstract

Non-bonded interaction of phytocompounds with SARS-CoV-2 MPro and RBD obtained after docking with Autodock Vina [A: Mpro-Balsaminone A; B: Mpro-Oleanderolide; C: Mpro-Proceragenin A; D: RBD-Balsaminone A; E: RBD-Oleanderolide; F: RBD-Proceragenin A ]The protein is shown in cartoon representation and the ligands are shown in stick format while interacting amino acids (shown in stick format) are labelled. The dotted lines indicate the hydrogen bonds.

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Keywords

Molecular docking
ADMET analysis
Molecular dynamic simulation
Phytocompounds
COVID-19

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