Phytochemicals of deciphered SARS-CoV-2 inhibition by targeting main proteases in molecular docking, simulation, and pharmacological analyses.

The COVID-19 pandemic is spreading rapidly due to the outbreak of novel coronavirus SARS-CoV-2 across the globe. Anti-COVID-19 drugs are urgently required in this situation. In this regard, the discovery of promising new anti-COVID-19 moieties is expected from traditional medicine. The study is aimed to discover phytochemicals of having anti-COVID-19 activity via inhibiting main proteases of SARS-CoV-2. Main proteases (M) of SARS-CoV-2 serve as a protuberant target for anti-COVID-19 drug discovery because it is a key enzyme of coronaviruses and has a pivotal role in mediating viral replication and transcription that makes it an attractive drug target. Recent studies indicated the utility of in the treatment of viral disorders like Dengue. Phytochemicals from were docked against SARS-CoV-2 main proteases (6LU7, 5R7Y, 5R7Z, 5R80, 5R81, 5R82) using the PyRx virtual screen tool and discovery studio visualizer. Further, molecular dynamics simulations were performed (for 100 ns) to see conformational stability for all complexes. Pharmacokinetic properties and drug-likeness prediction of selected phytoconstituents were also performed. Betulin, coclaurine, and quinic acid of were found promising with significant binding affinity to SARS-CoV-2 M in comparison to control. They have shown stable interactions with the amino acid residues present on the active site of most of the SARS-CoV-2 M and were found as promising anti-COVID-19 candidates. These compounds could be potential leads for the development of target-specific anti-COVID-19 therapeutics while ethnomedicinal uses of this herb could further needed for its detailed antiviral therapeutic exploration.Communicated by Ramaswamy H. Sarma.