Phytochemical and in silico studies for potential constituents from Centaurium spicatum as candidates against the SARS-CoV-2 main protease and RNA-dependent RNA polymerase

Abstract

In the present study, a new secoiridoid glycoside lisianthoside II 1, along with seven known compounds 2–8, were isolated from Centaurium spicatum L. In-silico molecular docking and molecular dynamic simulation against SARS-CoV-2 Main protease (M^pro) and RNA-dependent RNA polymerase (RdRp) were conducted. The affinity docking scores revealed that 8 is the best bound ligand to M^pro active site with binding energy of −14.9877 kcal/mol (RSMD = 1.16 Å), while 6 was the highest against RdRp (−16.9572 kcal/mol, RMSD = 1.01 Å). Moreover, the molecular dynamic simulation revealed that 8 with a (ΔG) of −7.9 kcal/mol (RMSD value of 2.6 Å) and 6 (RMSD value of 1.6 Å) and binding free energy (ΔG) of −7.1 kcal/mol achieved the highest stability over 50 ns of MDS inside the M^pro and RdRp enzyme’s active site, respectively. Hence, the isolated compounds could be a good lead for development of new leads targeting COVID-19.

Graphical Abstract

Keywords:

• Lisianthoside II
• SARS-CoV-2 main protease
• RNA-dependent RNA polymerase
• Centaurium spicatum

Acknowledgments

The authors acknowledge the Pharmacognosy and Chemistry of Natural Products Department, School of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan, for carrying out NMR analysis.

Disclosure statement

No potential conflict of interest was reported by the authors.

Funding

The author(s) reported there is no funding associated with the work featured in this article.