Targeting SARS-CoV-2 Spike Protein with Regional Ethnomedicinal Plant-derived Phytocompounds: A Comprehensive Molecular Docking, ADMET and MD Simulation Study

The achievement of efficient vaccine development for the SARS-CoV-2 virus marks a significant milestone, ultimately controlling the COVID-19 pandemic. However, the studies to find small molecules with potential SARS-CoV-2 inhibitory properties remained significant as there are not many treatment alternatives available. In this study, we studied biologically active phytocompounds present in regional ethnomedicinal plants like Lindera neesiana, Litsea cubeba and Zanthoxylum armatum DC using various computational techniques such as molecular docking, drug-likeness, ADMET study, MD simulation, etc. The SARS-CoV-2 spike protein’s RBD (PDB ID: 6m0j) has been docked with 107 phytocompounds. Top 5 phytocompounds with the best docking scores were further screened for their drug-likeness and ADMET properties. Following that, 100 ns MD simulations including PCA analysis were performed, providing additional evidence of the stability of the studied protein-ligand complexes. Binding free energies were also evaluated using the MM-GBSA method, which revealed spathulenol to exhibit the most favourable energy signifying its strong binding affinity and stability within the RBD of the spike protein. This in-silico study identifies the specific phytocompounds present in L. neesiana, L. cubeba and Z. armatum DC as a potential inhibitor of SARS-CoV-2 spike protein.