Potent Noncovalent Inhibitors of the Main Protease of SARS-CoV‑2 from Molecular Sculpting of the Drug Perampanel Guided by Free Energy Perturbation Calculations
Zhang CH, Stone EA, Deshmukh M, Ippolito JA, Ghahremanpour MM, Tirado-Rives J, Spasov KA, Zhang S, Takeo Y, Kudalkar SN, Liang Z, Isaacs F, Lindenbach B, Miller SJ, Anderson KS, Jorgensen WL. Potent Noncovalent Inhibitors of the Main Protease of SARS-CoV‑2 from Molecular Sculpting of the Drug Perampanel Guided by Free Energy Perturbation Calculations. ACS Central Science 2021, 7: 467-475. PMID: 33786375, PMCID: PMC7931627, DOI: 10.1021/acscentsci.1c00039.Peer-Reviewed Original ResearchFree energy perturbation calculationsX-ray crystal structurePotent noncovalent inhibitorMain proteaseHigh-resolution X-ray crystal structuresCell-based antiviral assaysComputational chemistryLigand complexesNoncovalent inhibitorsCrystal structureNonpeptidic inhibitorsLead optimizationDrug discoveryPerturbation calculationsNM ICPotent analoguesKinetic assaysPossible therapeutic significanceNoncovalentChemistryAnaloguesValuable guidanceCalculationsCompoundsComplexes