Phytoconstituents as potential therapeutic agents against COVID-19: a computational study on inhibition of SARS-CoV-2 main protease

The Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) has become a global health crisis, and the urgent need for effective treatments is evident. One potential target for COVID-19 therapeutics is the main protease (Mpro) of SARS‑CoV‑2, an essential enzyme for viral replication. Natural compounds have been explored as a source of potential inhibitors for Mpro due to their safety and availability. In this study, we employed a computational approach to screen a library of phytoconstituents and identified potential Mpro inhibitors based on their binding affinities and molecular interactions. The top-ranking compounds were further validated through molecular dynamics simulations (MDS) and free energy calculations. As a result of the above procedures, we identified two phytoconstituents, Khelmarin B and Neogitogenin, with appreciable binding affinity and specificity towards the Mpro binding pocket. Our results suggest that Khelmarin B and Neogitogenin could potentially serve as Mpro inhibitors and have the potential to be developed as COVID-19 therapeutics. Further experimental studies are required to confirm the efficacy and safety of these compounds. Communicated by Ramaswamy H. Sarma.