2023
Pharmacological 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 ResearchConceptsMSWI/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 resistance
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 ResearchConceptsExpression 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 entry
2021
Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes
Ravindra NG, Alfajaro MM, Gasque V, Huston NC, Wan H, Szigeti-Buck K, Yasumoto Y, Greaney AM, Habet V, Chow RD, Chen JS, Wei J, Filler RB, Wang B, Wang G, Niklason LE, Montgomery RR, Eisenbarth SC, Chen S, Williams A, Iwasaki A, Horvath TL, Foxman EF, Pierce RW, Pyle AM, van Dijk D, Wilen CB. Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes. PLOS Biology 2021, 19: e3001143. PMID: 33730024, PMCID: PMC8007021, DOI: 10.1371/journal.pbio.3001143.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionSARS-CoV-2Human bronchial epithelial cellsInterferon-stimulated genesCell state changesAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSyndrome coronavirus 2 infectionCell tropismCoronavirus 2 infectionCoronavirus disease 2019Onset of infectionCell-intrinsic expressionCourse of infectionAir-liquid interface culturesHost-viral interactionsBronchial epithelial cellsSingle-cell RNA sequencingCell typesIL-1Disease 2019Human airwaysDevelopment of therapeuticsDrug AdministrationViral replicationNonsteroidal Anti-inflammatory Drugs Dampen the Cytokine and Antibody Response to SARS-CoV-2 Infection
Chen JS, Alfajaro MM, Chow RD, Wei J, Filler RB, Eisenbarth SC, Wilen CB. Nonsteroidal Anti-inflammatory Drugs Dampen the Cytokine and Antibody Response to SARS-CoV-2 Infection. Journal Of Virology 2021, 95: 10.1128/jvi.00014-21. PMID: 33441348, PMCID: PMC8092681, DOI: 10.1128/jvi.00014-21.Peer-Reviewed Original ResearchSARS-CoV-2 infectionNonsteroidal anti-inflammatory drugsCOVID-19 pathogenesisSARS-CoV-2Anti-inflammatory drugsProduction of prostaglandinsCyclooxygenase-2Immune responseNSAID treatmentCyclooxygenase-1Enzymes cyclooxygenase-1Inflammatory responseAbility of NSAIDsAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSyndrome coronavirus 2 infectionSARS-CoV-2 vaccinationViral replicationPro-inflammatory cytokine responseCoronavirus 2 infectionExpression of angiotensinRelief of painPro-inflammatory cytokinesCoronavirus disease 2019 (COVID-19) pandemicHumoral immune response
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