In Silico Discovery of Small-Molecule Inhibitors Targeting SARS-CoV-2 Main Protease

The COVID-19 pandemic has caused severe health threat globally, and novel SARS-Cov-2 inhibitors are urgently needed for antiviral treatment. The main protease (M-pro) of the virus is one of the most effective and conserved targets for anti-SARS-CoV-2 drug development. In this study, we utilized a molecular docking-based virtual screening approach against the conserved catalytic site to identify small-molecule inhibitors of SARS-CoV-2 M-pro. Further biological evaluation helped us identify two compounds, AF-399/40713777 and AI-942/42301830, with moderate inhibitory activity. Besides that, the in silico data, including molecular dynamics (MD) simulation, binding free energy calculations, and AMDET profiles, suggested that these two hits could serve as the starting point for the future development of COVID-19 intervention treatments.

Automated summary

The COVID-19 pandemic has created a global health threat, necessitating the search for novel SARS-CoV-2 inhibitors for antiviral treatment. Through molecular docking-based virtual screening, this study identified two compounds with moderate inhibitory activity that could be potential starting points for the development of COVID-19 intervention treatments.