Maya Deshmukh
About
Research
Publications
2021
Optimization of Triarylpyridinone Inhibitors of the Main Protease of SARS-CoV‑2 to Low-Nanomolar Antiviral Potency
Zhang CH, Spasov KA, Reilly RA, Hollander K, Stone EA, Ippolito JA, Liosi ME, Deshmukh MG, Tirado-Rives J, Zhang S, Liang Z, Miller SJ, Isaacs F, Lindenbach BD, Anderson KS, Jorgensen WL. Optimization of Triarylpyridinone Inhibitors of the Main Protease of SARS-CoV‑2 to Low-Nanomolar Antiviral Potency. ACS Medicinal Chemistry Letters 2021, 12: 1325-1332. PMID: 34408808, PMCID: PMC8291137, DOI: 10.1021/acsmedchemlett.1c00326.Peer-Reviewed Original ResearchStructure-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 ResearchPotent Noncovalent Inhibitors of the Main Protease of SARS-CoV-2 from Molecular Sculpting of the Drug Perampanel Guided by Free Energy Perturbation Calculations
Zhang, C.-H. et al. 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).Peer-Reviewed Original Research
2019
Structural Insights into Curli CsgA Cross-β Fibril Architecture Inspire Repurposing of Anti-amyloid Compounds as Anti-biofilm Agents
Perov S, Lidor O, Salinas N, Golan N, Fligelman E, Deshmukh M, Willbold D, Landau M. Structural Insights into Curli CsgA Cross-β Fibril Architecture Inspire Repurposing of Anti-amyloid Compounds as Anti-biofilm Agents. PLOS Pathogens 2019, 15: e1007978. PMID: 31469892, PMCID: PMC6748439, DOI: 10.1371/journal.ppat.1007978.Peer-Reviewed Original ResearchConceptsDisease-associated amyloidsStructural insightsCross-seeded fibrillationMajor curli subunitBiofilm formationHost cell adhesionCurli amyloid fibrilsAmyloid-forming segmentAlzheimer's disease-associated amyloidAnti-amyloid compoundsCurli formationCurli subunitsPathological amyloidsAmyloidogenic regionsMicrobial sourcesEnvironmental stressorsAmyloid interactionsCell adhesionAnti-biofilm agentsΒ-sheetCsgANeurodegenerative diseasesSalmonella typhimuriumStructural linkStructural resemblance
2018
Amyloid by Design: Intrinsic Regulation of Microbial Amyloid Assembly.
Deshmukh M, Evans ML, Chapman MR. Amyloid by Design: Intrinsic Regulation of Microbial Amyloid Assembly. Journal Of Molecular Biology 2018, 430: 3631-3641. PMID: 30017921, PMCID: PMC6168361, DOI: 10.1016/j.jmb.2018.07.007.Peer-Reviewed Original Research
2016
The BR domain of PsrP interacts with extracellular DNA to promote bacterial aggregation; structural insights into pneumococcal biofilm formation
Schulte T, Mikaelsson C, Beaussart A, Kikhney A, Deshmukh M, Wolniak S, Pathak A, Ebel C, Löfling J, Fogolari F, Henriques-Normark B, Dufrêne YF, Svergun D, Nygren PÅ, Achour A. The BR domain of PsrP interacts with extracellular DNA to promote bacterial aggregation; structural insights into pneumococcal biofilm formation. Scientific Reports 2016, 6: 32371. PMID: 27582320, PMCID: PMC5007671, DOI: 10.1038/srep32371.Peer-Reviewed Original ResearchConceptsPneumococcal biofilm formationBiofilm formationExtracellular DNAPneumococcal serine-rich repeat proteinRich repeat proteinElectrophoretic mobility shift assaysHuman pathogen Streptococcus pneumoniaeAdhesive matrix moleculesMobility shift assaysMicrobial surface componentsMajor human pathogen Streptococcus pneumoniaeN-terminal regionNon-globular structuresSerine-rich repeat proteinPathogen Streptococcus pneumoniaeHelical DNA structureRepeat proteinsHeterologous expressionCircular dichroism studiesBR domainShift assaysStructural insightsBiofilm matrixIntermolecular β-sheetsBacterial aggregation
Links & Media
News
- March 18, 2021
Women's Mental Health Conference at Yale Finalizes Main Sessions for 2021 Conference
- February 10, 2021
Women's Mental Health Conference at Yale will Host Tarana Burke, Founder of #MeToo Movement, as 2021 Keynote Speaker
- September 01, 2020
Women's Mental Health Conference at Yale Sponsors Fundraiser for Family Justice Center