Structure-based virtual screening of novel natural products as chalcone derivatives against SARS-CoV-2 M^pro

Coronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2, has spread quickly around the world, causing a global pandemic. It has infected more than 500 million people as of April 28, 2022. Much research has been reported to stop the virus from spreading, but there are currently no approved medicines to treat COVID-19. In this work, a dataset of 142 natural products collected from various medicinal plants was used to perform structure-based virtual screening (SBVS) through the combined application of molecular docking and molecular dynamics (MD) simulation methods. First, the dataset of compounds was optimized using the density functional theory (DFT) approach. The optimized compounds were then submitted to the first screening, which was done by the pKCM web server to look for drug-likeness and the PyRx to look for binding affinity. Among the 142 natural substances, 10 compounds were selected for docking validation. Compounds that interact with CYS145 and LEU141, the essential catalytic residues, as well as compounds with binding affinities less than -8.0 kcal/mol, are considered promising anti-SARS-CoV-2 drug candidates. The top-ranked compounds were then evaluated by MD simulations and MM-GBSA method. These results could help researchers come up with new natural compounds that could be used to treat SARS-CoV-2.Communicated by Ramaswamy H. Sarma.