In silico exploration of Dakshina Kannada medicinal plants as anti-SARS-CoV-2 agents by molecular docking and simulation approaches

Aims: The rich ethno medicinal practices of Dakshina Kannada have received considerable attention, and many treatment methods have been documented. This work aimed to explore the traditional medicinal plants originating from Dakshina Kannada for their anti-SARS-CoV-2 activity by employing in silico methodologies. Methods: Virtual screening was carried out on Dakshina Kannada's plants known for their antiviral activities. Based on molecular docking scores, potent plants were shortlisted as Tinospora cordifolia, Nyctanthes arbortristis, Bacopa monnieri, Bombax ceiba, and Curcuma longa. Among these, the active plant Tinospora cordifolia possess the most potent phytochemicals. Molecular dynamics (MD) simulation and MM/GBSA calculations have been performed on cordifolioside A, syringin, and cordioside. Results: Initially, they were docked into the active site of SARS-CoV-2 protein. MD simulations were performed to investigate the various conformations and validate the docking results, revealing that cordifolioside A and syringin were more stable than cordioside. The stability of the phytoconstituents in complex with SARS-CoV-2 protein was steady throughout the 100 ns simulation time. Finally, the binding free energies were calculated using MM/GBSA method. The pharmacophore model has confirmed the hydrogen bond interactions, and PASS prediction determined their antiviral activities. Conclusion: Thus, the present study identified the most potent plant from Dakshina Kannada against the SARS-CoV-2 virus as Tinospora cordifolia with powerful phytochemicals (cordifolioside A, syringin and cordioside). Furthermore, in vitro and in vivo experiments are needed to provide experimental data to develop anti-SARS-CoV-2 drugs.