Investigation of Pyrrole Analogues Inhibition on Main Protease by Spectroscopic Analysis, Molecular Docking, and Enzyme Activity

The main protease (Mpro) is a cysteine enzyme and represents a vital target for antiviral drug screening. In this work, 25 pyrrole derivatives were synthesized and screened by enzyme activity experiments. Results indicate that six pyrrole derivatives can bind to Mpro and have an inhibitory effect on Mpro. The binding mode involves a static quenching process. Among them, 1d exhibits the highest binding affinity. The interactions between pyrrole derivatives and Mpro are investigated by spectra and molecular docking. The interaction between 1d and Mpro is spontaneous and enthalpy-driven. Hydrogen bonding is identified as the primary binding force for 1d. Furthermore, nitro groups are important for the binding between pyrrole analogs and Mpro. This study elucidates the mechanism of interactions and provides direction and valuable insights for developing novel Mpro inhibitors.