2020
An ACE2 Microbody Containing a Single Immunoglobulin Fc Domain Is a Potent Inhibitor of SARS-CoV-2
Tada T, Fan C, Chen JS, Kaur R, Stapleford KA, Gristick H, Dcosta BM, Wilen CB, Nimigean CM, Landau NR. An ACE2 Microbody Containing a Single Immunoglobulin Fc Domain Is a Potent Inhibitor of SARS-CoV-2. Cell Reports 2020, 33: 108528. PMID: 33326798, PMCID: PMC7705358, DOI: 10.1016/j.celrep.2020.108528.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAngiotensin-Converting Enzyme 2AnimalsAntiviral AgentsCOVID-19Disease Models, AnimalDisulfidesFemaleHEK293 CellsHumansImmunoglobulin Fc FragmentsMaleMice, TransgenicMicrobodiesProtein DomainsProtein MultimerizationSARS-CoV-2Spike Glycoprotein, CoronavirusVirionVirus InternalizationConceptsSARS-CoV-2Soluble ACE2Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionAcute respiratory syndrome coronavirus 2 infectionLive SARS-CoV-2Syndrome coronavirus 2 infectionCoronavirus 2 infectionSARS-CoV-2 spikeCoronavirus disease 2019SARS-CoV-2 spike proteinDisease 2019Enzyme 2Mouse modelFuture coronavirusesFc fusion proteinΒ-coronavirusViral variantsImmunoglobulin heavy chainSpike proteinACE2 ectodomainImmunoglobulin Fc domainFc domainVirusACE2Potent inhibitorGenome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection
Wei J, Alfajaro MM, DeWeirdt PC, Hanna RE, Lu-Culligan WJ, Cai WL, Strine MS, Zhang SM, Graziano VR, Schmitz CO, Chen JS, Mankowski MC, Filler RB, Ravindra NG, Gasque V, de Miguel FJ, Patil A, Chen H, Oguntuyo KY, Abriola L, Surovtseva YV, Orchard RC, Lee B, Lindenbach BD, Politi K, van Dijk D, Kadoch C, Simon MD, Yan Q, Doench JG, Wilen CB. Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection. Cell 2020, 184: 76-91.e13. PMID: 33147444, PMCID: PMC7574718, DOI: 10.1016/j.cell.2020.10.028.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2AnimalsCell LineChlorocebus aethiopsClustered Regularly Interspaced Short Palindromic RepeatsCoronavirusCoronavirus InfectionsCOVID-19Gene Knockout TechniquesGene Regulatory NetworksGenome-Wide Association StudyHEK293 CellsHMGB1 ProteinHost-Pathogen InteractionsHumansSARS-CoV-2Vero CellsVirus InternalizationConceptsSARS-CoV-2 infectionSARS-CoV-2Vesicular stomatitis virusGenome-wide CRISPR screenSWI/SNF chromatinSARS-CoV-2 host factorsAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionTherapeutic targetHost factorsCoronavirus disease 2019 (COVID-19) pathogenesisSyndrome coronavirus 2 infectionCRISPR screensHost genesGene productsMiddle East respiratory syndrome CoVCoronavirus 2 infectionGenetic hitsHuman cellsSARS-CoV-2 spikeNovel therapeutic targetPotential therapeutic targetVero E6 cellsSARS-CoV-1Small molecule antagonists
2013
Simultaneous zinc-finger nuclease editing of the HIV coreceptors ccr5 and cxcr4 protects CD4+ T cells from HIV-1 infection
Didigu CA, Wilen CB, Wang J, Duong J, Secreto AJ, Danet-Desnoyers GA, Riley JL, Gregory PD, June CH, Holmes MC, Doms RW. Simultaneous zinc-finger nuclease editing of the HIV coreceptors ccr5 and cxcr4 protects CD4+ T cells from HIV-1 infection. Blood 2013, 123: 61-69. PMID: 24162716, PMCID: PMC3879906, DOI: 10.1182/blood-2013-08-521229.Peer-Reviewed Original ResearchConceptsC chemokine receptor 5HIV-1 infectionT cellsHIV-1HIV coreceptor CCR5Chemokine receptor 5Humanized mouse modelDrug-free treatmentHIV-1 entryHIV coreceptorsPharmacologic blockadeCoreceptor CCR5Mouse modelCells engraftReceptor 5Gene-modified cellsCXCR4InfectionPrimary humanCoreceptorCD4CCR5Genetic inactivationVirusCells
2012
Transmitted/Founder and Chronic HIV-1 Envelope Proteins Are Distinguished by Differential Utilization of CCR5
Parker ZF, Iyer SS, Wilen CB, Parrish NF, Chikere KC, Lee FH, Didigu CA, Berro R, Klasse PJ, Lee B, Moore JP, Shaw GM, Hahn BH, Doms RW. Transmitted/Founder and Chronic HIV-1 Envelope Proteins Are Distinguished by Differential Utilization of CCR5. Journal Of Virology 2012, 87: 2401-2411. PMID: 23269796, PMCID: PMC3571396, DOI: 10.1128/jvi.02964-12.Peer-Reviewed Original ResearchConceptsCCR5 expression levelsF EnvsTransmitted/FounderHIV-1 envelope proteinCCR5 antagonist maravirocSingle genome amplificationExpression levelsSingle virus variantReplication-competent virusMVC resistanceFounder virusesChronic infectionCCR5 antagonistsT cellsHIV-1CCR5MaravirocControl virusPhysiologic levelsCCR5 conformationsVirus variantsEnvelope glycoproteinEnv proteinEnvInfection