Phytochemicals of Zingiberaceae family exhibit potentiality against SARS-CoV-2 main protease identified by a rational computer-aided drug design

Abstract

Coronavirus disease 2019 (COVID-19) has created huge social, economic and human health crises globally. Discovery of specific drugs has become a new challenge to the researcher. Structure-based virtual-screening of our in-house databank containing1102 phytochemicals of Zingiberaceae family was performed with main protease(M^pro), a crucial enzyme of SARS-CoV-2. Rigorous docking and ADME study of top-scored twenty hits resulted from VS was performed. Then 100 ns molecular dynamics followed by MMPBSA binding free energy(ΔG_bind) calculation of A280 and KZ133 was also performed. These two hits showed good interactions with crucial amino acid residues of M^pro HIS-41 and CYS-145, excellent ADME properties, fair ΔG_bind values (> ‒188.03 kj/mol), and average protein-ligand complex RMSD < apo-protein RMSD. Therefore, the seed extracts of Alpinia blepharocalyx and rhizome extracts Kaempferia angustifolia containing A280 and KZ133, respectively, may be useful against COVID-19 after the proper biological screening. These two novel scaffolds could be exploited as potent SARS-CoV-2-M^pro inhibitors.

Graphical Abstract

Keywords:

• COVID-19
• Zingiberaceae
• antiviral plant
• molecular docking
• ADME
• MD simulation

Acknowledgements

The author BD is thankful to AMBER Software Administrator for providing AMBER20 software facility in order to conduct MD simulation.

Disclosure statement

The authors declared that they have no conflict of interests.