Potent Noncovalent Inhibitors of the Main Protease of SARS-CoV-2 from Molecular Sculpting of the Drug Perampanel Guided by Free Energy Perturbation Calculations
Chunhui Zhang, Elizabeth A. Stone, M.G. Deshmukh, Joseph A. Ippolito, Mohammad Mehdi Ghahremanpour, Julian Tirado‐Rives, Krasimir A. Spasov, Shuo Zhang, Yuka Takeo, Shalley N. Kudalkar, Zhuobin Liang, Farren J. Isaacs, Brett D. Lindenbach, Scott J. Miller, Karen S. Anderson, William L. Jorgensen
Abstract
. Results of cell-based antiviral assays further demonstrated the potential of the compounds for treatment of COVID-19. In addition to the possible therapeutic significance, the work clearly demonstrates the power of computational chemistry for drug discovery, especially FEP-guided lead optimization.
Topics & Concepts
PerampanelFree energy perturbationChemistryCombinatorial chemistryProteaseSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Coronavirus disease 2019 (COVID-19)IC50StereochemistryComputational chemistryEnzymeMolecular dynamicsBiochemistryPharmacologyIn vitroBiologyInfectious disease (medical specialty)PathologyAdverse effectMedicineDiseaseComputational Drug Discovery MethodsProtein Structure and DynamicsSARS-CoV-2 and COVID-19 Research