Identification of a Putative SARS-CoV-2 Main Protease Inhibitor through In Silico Screening of Self-Designed Molecular Library

There have been outbreaks of SARS-CoV-2 around the world for over three years, and its variants continue to evolve. This has become a major global health threat. The main protease (Mpro, also called 3CLpro) plays key role in viral replication proliferation, making it an attractive drug target. Here, we identified novel potential inhibitor Mpro, by applying virtual screening hundreds nilotinib-structure-like compounds that designed synthesized. screened were assessed using SP docking, XP MM-GBSA analysis, IFD MD simulation, ADME/T prediction, then enzymatic assay vitro. We finally compound V291 as Mpro inhibitor, with high docking affinity enzyme inhibitory activity. Moreover, results indicate His41 is favorable amino acid pi-pi interactions, while Glu166 can participate salt-bridge formation protonated primary or secondary amines molecules. Thus, reported here are capable engaging acids ligand-receptor interactions. A pharmacophore analysis further validates this assertion.