2021
Structure-guided design of a perampanel-derived pharmacophore targeting the SARS-CoV-2 main protease
Deshmukh MG, Ippolito JA, Zhang CH, Stone EA, Reilly RA, Miller SJ, Jorgensen WL, Anderson KS. Structure-guided design of a perampanel-derived pharmacophore targeting the SARS-CoV-2 main protease. Structure 2021, 29: 823-833.e5. PMID: 34161756, PMCID: PMC8218531, DOI: 10.1016/j.str.2021.06.002.Peer-Reviewed Original ResearchConceptsMain proteaseSARS-CoV-2 main proteaseActive site flexibilityDetailed structural insightsStructure-activity relationshipsInhibitor design effortsLow micromolar rangeActive site cysteineChemical scaffoldsLow nanomolar rangeCovalent adductsStructure-guided designCrystal structureStructural insightsPharmacophoreAdductsAttractive targetScaffoldsCysteineAnaloguesMechanism of actionSupRangeStructurePotent 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
2020
Identification of 14 Known Drugs as Inhibitors of the Main Protease of SARS-CoV‑2
Ghahremanpour MM, Tirado-Rives J, Deshmukh M, Ippolito JA, Zhang CH, de Vaca I, Liosi ME, Anderson KS, Jorgensen WL. Identification of 14 Known Drugs as Inhibitors of the Main Protease of SARS-CoV‑2. ACS Medicinal Chemistry Letters 2020, 11: 2526-2533. PMID: 33324471, PMCID: PMC7605328, DOI: 10.1021/acsmedchemlett.0c00521.Peer-Reviewed Original Research