2024
Structure and inhibition of SARS-CoV-2 spike refolding in membranes
Grunst M, Qin Z, Dodero-Rojas E, Ding S, Prévost J, Chen Y, Hu Y, Pazgier M, Wu S, Xie X, Finzi A, Onuchic J, Whitford P, Mothes W, Li W. Structure and inhibition of SARS-CoV-2 spike refolding in membranes. Science 2024, 385: 757-765. PMID: 39146425, PMCID: PMC11449073, DOI: 10.1126/science.adn5658.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2Antibodies, NeutralizingAntibodies, ViralBetacoronavirusCell MembraneCOVID-19Cryoelectron MicroscopyElectron Microscope TomographyHumansMolecular Dynamics SimulationPeptidyl-Dipeptidase AProtein DomainsProtein MultimerizationProtein RefoldingSARS-CoV-2Spike Glycoprotein, CoronavirusVirus InternalizationFirst encounter with SARS-CoV-2: immune portraits of COVID susceptibility
Israelow B, Iwasaki A. First encounter with SARS-CoV-2: immune portraits of COVID susceptibility. Nature 2024, 631: 33-35. PMID: 38898251, DOI: 10.1038/d41586-024-01644-x.Peer-Reviewed Original Research
2023
Beluga whale and bottlenose dolphin ACE2 proteins allow cell entry mediated by spike protein from three variants of SARS-CoV-2
Stone H, Unal E, Romano T, Turner P. Beluga whale and bottlenose dolphin ACE2 proteins allow cell entry mediated by spike protein from three variants of SARS-CoV-2. Biology Letters 2023, 19: 20230321. PMID: 38053365, PMCID: PMC10698476, DOI: 10.1098/rsbl.2023.0321.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2AnimalsBeluga WhaleBottle-Nosed DolphinCOVID-19HumansSARS-CoV-2Spike Glycoprotein, CoronavirusVirus InternalizationConceptsAngiotensin-converting enzyme 2Beluga whalesCell entrySpike proteinSpillover of SARS-CoV-2SARS-CoV-2 spike proteinWuhan-Hu-1Formation of social groupsSARS-CoV-2Susceptibility to virus infectionHost individualsAnimal hostsVariants of SARS-CoV-2Pandemic isolatesBottlenose dolphinsACE2 proteinCellular receptorsContact with humansBelugaPotential threatDolphinsProteinAnimal reservoirsEnzyme 2Mammal reservoirsSialylated Glycan Bindings from SARS-CoV-2 Spike Protein to Blood and Endothelial Cells Govern the Severe Morbidities of COVID-19
Scheim D, Vottero P, Santin A, Hirsh A. Sialylated Glycan Bindings from SARS-CoV-2 Spike Protein to Blood and Endothelial Cells Govern the Severe Morbidities of COVID-19. International Journal Of Molecular Sciences 2023, 24: 17039. PMID: 38069362, PMCID: PMC10871123, DOI: 10.3390/ijms242317039.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2AnimalsCommon ColdCOVID-19Endothelial CellsHumansHypoxiaMammalsMorbidityPolysaccharidesPost-Acute COVID-19 SyndromeSARS-CoV-2Spike Glycoprotein, CoronavirusConceptsSARS-CoV-2 spike proteinRed blood cellsCOVID-19Severe COVID-19 patientsSpike proteinSevere COVID-19COVID-19 correlatesCOVID-19 patientsCommon cold infectionsCOVID-19 morbidityLong-COVID patientsFuture therapeutic strategiesSARS-CoV-2Key risk factorsKey morbiditiesSurface of plateletsSevere morbidityClinical efficacyVascular damageViral loadMicrovascular occlusionRisk factorsCOVID patientsClinical studiesClinical susceptibilityReply to: Targeted protein S-nitrosylation of ACE2 inhibits SARS-CoV-2 infection
Oh C, Piña-Crespo J, Talantova M, Carnevale L, Stoneham C, Lewinski M, Guatelli J, Lipton S. Reply to: Targeted protein S-nitrosylation of ACE2 inhibits SARS-CoV-2 infection. Nature Chemical Biology 2023, 19: 1306-1308. PMID: 37798355, DOI: 10.1038/s41589-023-01425-z.Peer-Reviewed Original ResearchThe KDM6A-KMT2D-p300 axis regulates susceptibility to diverse coronaviruses by mediating viral receptor expression
Wei J, Alfajaro M, Cai W, Graziano V, Strine M, Filler R, Biering S, Sarnik S, Patel S, Menasche B, Compton S, Konermann S, Hsu P, Orchard R, Yan Q, Wilen C. The KDM6A-KMT2D-p300 axis regulates susceptibility to diverse coronaviruses by mediating viral receptor expression. PLOS Pathogens 2023, 19: e1011351. PMID: 37410700, PMCID: PMC10325096, DOI: 10.1371/journal.ppat.1011351.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2AnimalsCOVID-19Dipeptidyl Peptidase 4Histone DemethylasesHumansMiceMiddle East Respiratory Syndrome CoronavirusReceptors, VirusSARS-CoV-2ConceptsMouse hepatitis virusReceptor expressionTherapeutic targetMERS-CoVMajor SARS-CoV-2 variantsPrimary human airwaySARS-CoV-2 variantsNovel therapeutic targetViral receptor expressionSARS-CoV-2Histone methyltransferase KMT2DIntestinal epithelial cellsCoronavirus SusceptibilityDiverse coronavirusesHistone demethylase KDM6ADPP4 expressionCoronavirus receptorsHost determinantsHepatitis virusHuman airwaysSARS-CoVSmall molecule inhibitionViral entryPotential drug targetsViral receptorsDYRK1A promotes viral entry of highly pathogenic human coronaviruses in a kinase-independent manner
Strine M, Cai W, Wei J, Alfajaro M, Filler R, Biering S, Sarnik S, Chow R, Patil A, Cervantes K, Collings C, DeWeirdt P, Hanna R, Schofield K, Hulme C, Konermann S, Doench J, Hsu P, Kadoch C, Yan Q, Wilen C. DYRK1A promotes viral entry of highly pathogenic human coronaviruses in a kinase-independent manner. PLOS Biology 2023, 21: e3002097. PMID: 37310920, PMCID: PMC10263356, DOI: 10.1371/journal.pbio.3002097.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2AnimalsCOVID-19Dipeptidyl Peptidase 4HumansMiddle East Respiratory Syndrome CoronavirusSARS-CoV-2Severe acute respiratory syndrome-related coronavirusVirus InternalizationConceptsGenome-wide CRISPR/Cas9 screenCRISPR/Cas9 screenPathogenic human coronavirusesKinase-independent mannerRegulated kinase 1AProviral host factorNovel drug targetsMultiple cell typesDNA accessibilityHost factorsKinase functionHuman coronavirusesHost genesDistal enhancerNovel regulatorCas9 screenKinase 1AGene expressionNeuronal developmentDYRK1ADrug targetsDiverse coronavirusesProviral activityCell typesSevere acute respiratory syndrome coronavirus 2Pharmacological disruption of mSWI/SNF complex activity restricts SARS-CoV-2 infection
Wei J, Patil A, Collings C, Alfajaro M, Liang Y, Cai W, Strine M, Filler R, DeWeirdt P, Hanna R, Menasche B, Ökten A, Peña-Hernández M, Klein J, McNamara A, Rosales R, McGovern B, Luis Rodriguez M, García-Sastre A, White K, Qin Y, Doench J, Yan Q, Iwasaki A, Zwaka T, Qi J, Kadoch C, Wilen C. Pharmacological disruption of mSWI/SNF complex activity restricts SARS-CoV-2 infection. Nature Genetics 2023, 55: 471-483. PMID: 36894709, PMCID: PMC10011139, DOI: 10.1038/s41588-023-01307-z.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2ChromatinCOVID-19DNA HelicasesHumansNuclear ProteinsSARS-CoV-2Transcription FactorsConceptsMSWI/SNF complexesAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionHost-directed therapeutic targetSyndrome coronavirus 2 infectionSARS-CoV-2 infectionSWItch/Sucrose Non-Fermentable (SWI/SNF) chromatinSARS-CoV-2 susceptibilityNon-fermentable (SWI/SNF) chromatinCoronavirus 2 infectionEnzyme 2 (ACE2) expressionSARS-CoV-2 variantsHuman cell typesPrimary human cell typesAirway epithelial cellsDrug-resistant variantsNew drug targetsChromatin accessibilitySNF complexACE2 locusACE2 expressionFactor complexHost determinantsTherapeutic targetConfer resistanceUnique DUOX2+ACE2+ small cholangiocytes are pathogenic targets for primary biliary cholangitis
Li X, Li Y, Xiao J, Wang H, Guo Y, Mao X, Shi P, Hou Y, Zhang X, Zhao N, Zheng M, He Y, Ding J, Tan Y, Liao M, Li L, Peng Y, Li X, Pan Q, Xie Q, Li Q, Li J, Li Y, Chen Z, Huang Y, Assis D, Cai S, Boyer J, Huang X, Tang C, Liu X, Peng S, Chai J. Unique DUOX2+ACE2+ small cholangiocytes are pathogenic targets for primary biliary cholangitis. Nature Communications 2023, 14: 29. PMID: 36759512, PMCID: PMC9911648, DOI: 10.1038/s41467-022-34606-w.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2AnimalsDual OxidasesEpithelial CellsHumansLiver Cirrhosis, BiliaryMiceConceptsPrimary biliary cholangitisPrimary biliary cholangitis patientsBiliary cholangitisEtiology of primary biliary cholangitisScRNA-seqPathogenic targetsSeverity of diseaseSingle-cell RNA sequencingAMA-M2PBC patientsAutoantibody levelsPolymeric immunoglobulin receptorMemory BMultiplex immunofluorescenceCholangiocyte injuryPlasma cellsAutoimmune diseasesRNAscope analysisCholangiocytesImmunoglobulin receptorBile formationPatientsTherapeutic interventionsMultiplexed IFRNA sequencing
2022
LRRC15 inhibits SARS-CoV-2 cellular entry in trans
Song J, Chow RD, Peña-Hernández MA, Zhang L, Loeb SA, So EY, Liang OD, Ren P, Chen S, Wilen CB, Lee S. LRRC15 inhibits SARS-CoV-2 cellular entry in trans. PLOS Biology 2022, 20: e3001805. PMID: 36228039, PMCID: PMC9595563, DOI: 10.1371/journal.pbio.3001805.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2COVID-19HumansMembrane ProteinsProtein BindingSARS-CoV-2Spike Glycoprotein, CoronavirusConceptsExpression of LRRC15Receptor-binding domainViral entryAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSARS-CoV-2 cellular entrySyndrome coronavirus 2 infectionSARS-CoV-2 entrySpike-mediated entryCoronavirus 2 infectionCOVID-19 patientsCellular entry factorsSARS-CoV-2Attachment factorsACE2-negative cellsEnzyme 2Receptor angiotensinEntry factorsProtective roleLRRC15Spike proteinSame cell typeCRISPR activation screensACE2Cellular entryTargeted protein S-nitrosylation of ACE2 inhibits SARS-CoV-2 infection
Oh C, Nakamura T, Beutler N, Zhang X, Piña-Crespo J, Talantova M, Ghatak S, Trudler D, Carnevale L, McKercher S, Bakowski M, Diedrich J, Roberts A, Woods A, Chi V, Gupta A, Rosenfeld M, Kearns F, Casalino L, Shaabani N, Liu H, Wilson I, Amaro R, Burton D, Yates J, Becker C, Rogers T, Chatterjee A, Lipton S. Targeted protein S-nitrosylation of ACE2 inhibits SARS-CoV-2 infection. Nature Chemical Biology 2022, 19: 275-283. PMID: 36175661, PMCID: PMC10127945, DOI: 10.1038/s41589-022-01149-6.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2COVID-19HumansPeptidyl-Dipeptidase AProtein BindingSARS-CoV-2ConceptsSARS-CoV-2 infectionViral entrySevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Coronavirus disease 2019 (COVID-19) pandemicSyndrome coronavirus 2Prevention of infectionSARS-CoV-2 spike proteinDisease 2019 pandemicSpread of infectionCoronavirus 2Channel blockadeS-nitrosylationEnzyme 2Binding of ACE2InfectionSpike proteinACE2Envelope proteinProtein S-nitrosylationIon channelsNon-toxic compoundsNovel avenuesAngiotensinA Retinol Derivative Inhibits SARS-CoV-2 Infection by Interrupting Spike-Mediated Cellular Entry
Tong L, Wang L, Liao S, Xiao X, Qu J, Wu C, Zhu Y, Tai W, Huang Y, Wang P, Li L, Zhang R, Xiang Y, Cheng G. A Retinol Derivative Inhibits SARS-CoV-2 Infection by Interrupting Spike-Mediated Cellular Entry. MBio 2022, 13: e01485-22. PMID: 35862773, PMCID: PMC9426596, DOI: 10.1128/mbio.01485-22.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2Antiviral AgentsCOVID-19 Drug TreatmentHumansPeptidyl-Dipeptidase AProtein BindingSARS-CoV-2Spike Glycoprotein, CoronavirusTretinoinVitamin AConceptsSARS-CoV-2 variantsSARS-CoV-2 infectionPotent antiviral activitySevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Inhibits SARS-CoV-2 infectionAntiviral activityRespiratory syndrome coronavirus 2Retinoic acidLower respiratory tractSyndrome coronavirus 2Coronavirus disease 2019Multiple organ systemsVitamin A derivativesCOVID-19 diseaseSpike protein trimerS trimerCoronavirus 2Respiratory tractDisease 2019Vitamin AActive metaboliteOrgan systemsEtiological agentTherapeutic antibodiesCOVID-19 & differential effects in twins: Insights from Placenta Pathology
Moriarty K, Yu M, Hussain N, Zgutka K, Sanders MM, Harigopal M, Wang J, Wang X, Hui P, Liu C, Sink D, Shields A. COVID-19 & differential effects in twins: Insights from Placenta Pathology. Placenta 2022, 124: 62-66. PMID: 35640456, PMCID: PMC9121647, DOI: 10.1016/j.placenta.2022.05.014.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2COVID-19FemaleHumansInfectious Disease Transmission, VerticalMalePlacentaPregnancyPregnancy Complications, InfectiousSARS-CoV-2ConceptsSARS-CoV-2Perinatal lossCOVID-19Adverse pregnancy outcomesMaternal-fetal interfaceTime of infectionDifferential effectsPregnancy outcomesPremature deliveryFetal interfaceGestational agePlacenta pathologyTwin pregnanciesMembranous expressionFemale fetusesFetal sexViral detection methodsViral receptorsFemale twinsTissue resultsPregnancyPlacentaTask ForceSuccumbedFetusesInflammasome activation in infected macrophages drives COVID-19 pathology
Sefik E, Qu R, Junqueira C, Kaffe E, Mirza H, Zhao J, Brewer JR, Han A, Steach HR, Israelow B, Blackburn HN, Velazquez SE, Chen YG, Halene S, Iwasaki A, Meffre E, Nussenzweig M, Lieberman J, Wilen CB, Kluger Y, Flavell RA. Inflammasome activation in infected macrophages drives COVID-19 pathology. Nature 2022, 606: 585-593. PMID: 35483404, PMCID: PMC9288243, DOI: 10.1038/s41586-022-04802-1.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2AnimalsCOVID-19HumansInflammasomesInterleukin-1Interleukin-18LungMacrophagesMiceNLR Family, Pyrin Domain-Containing 3 ProteinPneumoniaPyroptosisReceptors, IgGSARS-CoV-2ConceptsInflammasome activationLung inflammationInflammatory responseInfected macrophagesSARS-CoV-2 infectionHuman macrophagesChronic lung pathologyPersistent lung inflammationSevere COVID-19Immune inflammatory responseInflammatory cytokine productionHumanized mouse modelNLRP3 inflammasome pathwayCOVID-19 pathologyCOVID-19SARS-CoV-2Productive viral cycleHyperinflammatory stateChronic stageIL-18Cytokine productionInflammatory cytokinesLung pathologyInflammasome pathwayInterleukin-1Extracellular vimentin is an attachment factor that facilitates SARS-CoV-2 entry into human endothelial cells
Amraei R, Xia C, Olejnik J, White M, Napoleon M, Lotfollahzadeh S, Hauser B, Schmidt A, Chitalia V, Mühlberger E, Costello C, Rahimi N. Extracellular vimentin is an attachment factor that facilitates SARS-CoV-2 entry into human endothelial cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2113874119. PMID: 35078919, PMCID: PMC8833221, DOI: 10.1073/pnas.2113874119.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionHuman endothelial cellsSARS-CoV-2 entrySARS-CoV-2S-protein interactionEndothelial cellsIdentification of vimentinShRNA-mediated knockdownIntermediate filament proteinsBinding of vimentinHEK-293 cellsAttachment factorsViral entrySARS-CoV-2 S proteinDevelopment of therapeuticsExtracellular vimentinS protein receptorInfectious SARS-CoV-2Host cellsCellular componentsCoexpression of vimentinFilament proteinsPrimary entry receptorSARS-CoV-2 spike proteinS proteinDevelopment and utilization of a surrogate SARS-CoV-2 viral neutralization assay to assess mRNA vaccine responses
Wisnewski AV, Liu J, Lucas C, Klein J, Iwasaki A, Cantley L, Fazen L, Luna J, Slade M, Redlich CA. Development and utilization of a surrogate SARS-CoV-2 viral neutralization assay to assess mRNA vaccine responses. PLOS ONE 2022, 17: e0262657. PMID: 35041700, PMCID: PMC8765639, DOI: 10.1371/journal.pone.0262657.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2Antibodies, NeutralizingAntibodies, ViralCOVID-19COVID-19 VaccinesEnzyme-Linked Immunosorbent AssayFemaleHumansMalemRNA VaccinesSARS-CoV-2Vaccines, SyntheticConceptsPlaque reduction neutralization testCOVID-19 patientsVaccine responsesRecovered COVID-19 patientsSARS-CoV-2 immunityBooster vaccine dosesMRNA vaccine responsePost-vaccine seraCompetitive ELISAEnzyme 2 (ACE2) receptorReduction neutralization testType of vaccineSARS-CoV-2 spike protein receptorSpike protein receptorVaccine seraVaccine recipientsPost vaccinationVaccinated individualsVaccine dosesViral culturePrior historyViral neutralizationNeutralization testBooster shotsPost vaccine
2021
Supermeres are functional extracellular nanoparticles replete with disease biomarkers and therapeutic targets
Zhang Q, Jeppesen DK, Higginbotham JN, Graves-Deal R, Trinh VQ, Ramirez MA, Sohn Y, Neininger AC, Taneja N, McKinley ET, Niitsu H, Cao Z, Evans R, Glass SE, Ray KC, Fissell WH, Hill S, Rose KL, Huh WJ, Washington MK, Ayers GD, Burnette DT, Sharma S, Rome LH, Franklin JL, Lee YA, Liu Q, Coffey RJ. Supermeres are functional extracellular nanoparticles replete with disease biomarkers and therapeutic targets. Nature Cell Biology 2021, 23: 1240-1254. PMID: 34887515, PMCID: PMC8656144, DOI: 10.1038/s41556-021-00805-8.Peer-Reviewed Original ResearchConceptsSmall extracellular vesiclesTherapeutic targetExtracellular vesiclesHepatic lipidsCardiovascular diseaseCetuximab resistanceMultiple cancersAlzheimer's diseaseDiseaseLactate secretionDisease biomarkersBiomarkersExtracellular RNAIntense investigationHuman diseasesGreater uptakeVivoCancerSecretionThe alpha/B.1.1.7 SARS-CoV-2 variant exhibits significantly higher affinity for ACE-2 and requires lower inoculation doses to cause disease in K18-hACE2 mice
Bayarri-Olmos R, Johnsen L, Idorn M, Reinert L, Rosbjerg A, Vang S, Hansen C, Helgstrand C, Bjelke J, Bak-Thomsen T, Paludan S, Garred P, Skjoedt M. The alpha/B.1.1.7 SARS-CoV-2 variant exhibits significantly higher affinity for ACE-2 and requires lower inoculation doses to cause disease in K18-hACE2 mice. ELife 2021, 10: e70002. PMID: 34821555, PMCID: PMC8635972, DOI: 10.7554/elife.70002.Peer-Reviewed Original ResearchConceptsK18-hACE2 miceTransgenic hACE2 miceFaster disease progressionAlpha/B.SARS-CoV-2 isolatesVariants of concernSARS-CoV-2 lineagesHACE2 miceConvalescent individualsCOVID-19 casesDisease progressionEnzyme 2Low doseB.1.1.7 variantAntibody neutralizationHuman angiotensinInoculation dosesMonoclonal antibodiesNew COVID-19 casesACE-2Lower inoculation dosesWinter 2021MiceN501Y variantsSeverityThe immunologic response to severe acute respiratory syndrome coronavirus 2.
Le N, Kaman K, Martin H, Mullur J, Stenehjem K, Coomar L, Bahar B, Dutta M, Izurieta R, Brooks J. The immunologic response to severe acute respiratory syndrome coronavirus 2. Allergy & Asthma Proceedings 2021, 42: 495-505. PMID: 34871157, DOI: 10.2500/aap.2021.42.210077.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAngiotensin-Converting Enzyme 2COVID-19Disease SusceptibilityHumansImmune SystemImmunity, InnatePandemicsSARS-CoV-2Spike Glycoprotein, CoronavirusConceptsHuman immune systemImmune systemAdaptive immune responses to SARS-CoV-2 infectionSARS-CoV-2Immune response to SARS-CoV-2 infectionResponse to SARS-CoV-2 infectionSARS-CoV-2 infectionEnglish-language articlesInnate immune systemCourse of infectionInflammatory overreactionInnate immune pathwaysProportion of infectionsSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Immune modulationProphylactic interventionsRespiratory syndrome coronavirus 2Diagnostic strategiesImmunological responsePreventing severe diseaseSevere diseaseSyndrome coronavirus 2Immune pathwaysPatient recoveryFunctional Effects of Receptor-Binding Domain Mutations of SARS-CoV-2 B.1.351 and P.1 Variants
Bayarri-Olmos R, Jarlhelt I, Johnsen L, Hansen C, Helgstrand C, Bjelke J, Matthiesen F, Nielsen S, Iversen K, Ostrowski S, Bundgaard H, Frikke-Schmidt R, Garred P, Skjoedt M. Functional Effects of Receptor-Binding Domain Mutations of SARS-CoV-2 B.1.351 and P.1 Variants. Frontiers In Immunology 2021, 12: 757197. PMID: 34691078, PMCID: PMC8529273, DOI: 10.3389/fimmu.2021.757197.Peer-Reviewed Original Research
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