De novo Design of SARS-CoV-2 Main Protease Inhibitors
Nynke A. Vepřek, Zisis V. Peitsinis, Yingkai Zhang, Dirk H. Trauner, Christian Fischer, Klaus-Peter Rühmann, Chao Yang, Jessica N. Spradlin, Dustin Dovala, Daniel K. Nomura · Synlett · 2021
Abstract The COVID-19 pandemic prompted many scientists to investigate remedies against SARS-CoV-2 and related viruses that are likely to appear in the future. As the main protease of the virus, MPro, is highly conserved among coronaviruses, it has emerged as a prime target for developing inhibitors. Using a combination of virtual screening and molecular modeling, we identified small molecules that were easily accessible and could be quickly diversified. Biochemical assays confirmed a class of pyridones as low micromolar noncovalent inhibitors of the viral main protease.