2024
Proof-of-concept studies with a computationally designed Mpro inhibitor as a synergistic combination regimen alternative to Paxlovid
Papini C, Ullah I, Ranjan A, Zhang S, Wu Q, Spasov K, Zhang C, Mothes W, Crawford J, Lindenbach B, Uchil P, Kumar P, Jorgensen W, Anderson K. Proof-of-concept studies with a computationally designed Mpro inhibitor as a synergistic combination regimen alternative to Paxlovid. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2320713121. PMID: 38621119, PMCID: PMC11046628, DOI: 10.1073/pnas.2320713121.Peer-Reviewed Original ResearchConceptsDirect-acting antiviralsSARS-CoV-2Lack of off-target effectsIn vitro pharmacological profileTreatment of patientsDevelopment of severe symptomsPharmacological propertiesDrug-drug interactionsSARS-CoV-2 infectionProof-of-concept studySARS-CoV-2 M<sup>pro</sup>.Combination regimenImmunocompromised patientsLead compoundsSARS-CoV-2 main proteaseOral doseActive drugTreat infectionsPharmacological profileSARS-CoV-2 MPotential preclinical candidateOff-target effectsPatientsComplete recoveryCapsule formulationPrior Influenza Infection Mitigates SARS-CoV-2 Disease in Syrian Hamsters
Di Pietro C, Haberman A, Lindenbach B, Smith P, Bruscia E, Allore H, Vander Wyk B, Tyagi A, Zeiss C. Prior Influenza Infection Mitigates SARS-CoV-2 Disease in Syrian Hamsters. Viruses 2024, 16: 246. PMID: 38400021, PMCID: PMC10891789, DOI: 10.3390/v16020246.Peer-Reviewed Original ResearchConceptsTransient gene expressionSARS-CoV-2Viral replication pathwayReplication pathwayAntiviral pathwaysEndemism patternsUpregulation of innateGene expressionQuantitative RT-PCRMitigated weight lossDual-infected animalsSARS-CoV-2 viral loadSARS-CoV-2 infectionSyrian hamstersSeasonal infection ratesSARS-CoV-2 inoculationLungs of animalsIndividual virusesSARS-CoV-2 diseaseUpper respiratory tractH1N1 infectionRT-PCRBronchoalveolar lavageViral loadCytokine levels
2021
Restriction of SARS-CoV-2 replication by targeting programmed −1 ribosomal frameshifting
Sun Y, Abriola L, Niederer RO, Pedersen SF, Alfajaro MM, Silva Monteiro V, Wilen CB, Ho YC, Gilbert WV, Surovtseva YV, Lindenbach BD, Guo JU. Restriction of SARS-CoV-2 replication by targeting programmed −1 ribosomal frameshifting. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2023051118. PMID: 34185680, PMCID: PMC8256030, DOI: 10.1073/pnas.2023051118.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 replicationSARS-CoV-2Severe acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Syndrome coronavirus 2Vero E6 cellsHigh-throughput compound screenOpen reading frame 1bEffective antiviral strategiesCoronavirus 2E6 cellsAntiviral strategiesViral gene expressionCompound screenFluoroquinolone antibacterialsFrame 1bGene expression
2016
Vaginal Exposure to Zika Virus during Pregnancy Leads to Fetal Brain Infection
Yockey LJ, Varela L, Rakib T, Khoury-Hanold W, Fink SL, Stutz B, Szigeti-Buck K, Van den Pol A, Lindenbach BD, Horvath TL, Iwasaki A. Vaginal Exposure to Zika Virus during Pregnancy Leads to Fetal Brain Infection. Cell 2016, 166: 1247-1256.e4. PMID: 27565347, PMCID: PMC5006689, DOI: 10.1016/j.cell.2016.08.004.Peer-Reviewed Original ResearchMeSH KeywordsAbortion, HabitualAnimalsBrainBrain DiseasesDisease Models, AnimalFemaleFetal Growth RetardationInterferon Regulatory Factor-3MiceMice, Inbred C57BLMice, Mutant StrainsPregnancyPregnancy Complications, InfectiousReceptor, Interferon alpha-betaVaginaVirus ReplicationZika VirusZika Virus InfectionConceptsZika virusFetal brain infectionFetal growth restrictionLocal viral replicationWild-type miceType I interferon receptorZIKV challengeTranscription factor IRF3Vaginal exposureGenital mucosaBrain infectionWT miceEarly pregnancyZIKV infectionGrowth restrictionPregnant damsVaginal infectionsZIKV replicationFetal brainMouse modelIFN pathwayVaginal tractUnborn fetusViral replicationDisease consequences
2013
The ins and outs of hepatitis C virus entry and assembly
Lindenbach BD, Rice CM. The ins and outs of hepatitis C virus entry and assembly. Nature Reviews Microbiology 2013, 11: 688-700. PMID: 24018384, PMCID: PMC3897199, DOI: 10.1038/nrmicro3098.Peer-Reviewed Original ResearchConceptsHCV particlesRNA virusesPositive-strand RNA virusesSignal transduction eventsSerum lipoproteinsCell surface proteinsHepatitis C Virus EntryNumerous cell surface proteinsNon-structural proteinsNew structural informationC virus entrySecretory pathwayTransduction eventsUncharacterized mechanismMembrane fusionHCV particle assemblyCellular processingSurface proteinsC virus
2011
Structural Insights into RNA Recognition by RIG-I
Luo D, Ding SC, Vela A, Kohlway A, Lindenbach BD, Pyle AM. Structural Insights into RNA Recognition by RIG-I. Cell 2011, 147: 409-422. PMID: 22000018, PMCID: PMC3222294, DOI: 10.1016/j.cell.2011.09.023.Peer-Reviewed Original ResearchConceptsPathogen-associated molecular patternsTerminal regulatory domainProtein familyRegulatory domainProtein domainsInsertion domainRNA recognitionMolecular basisATP hydrolysisStructural insightsIntracellular RIGRNAMolecular patternsMotor domainLike receptorsAntiviral immune responseViral RNANanomechanical FunctionDomainHelicasesComplex interplayHelicaseCladeHel2DsRNA
2006
Cell culture-grown hepatitis C virus is infectious in vivo and can be recultured in vitro
Lindenbach BD, Meuleman P, Ploss A, Vanwolleghem T, Syder AJ, McKeating JA, Lanford RE, Feinstone SM, Major ME, Leroux-Roels G, Rice CM. Cell culture-grown hepatitis C virus is infectious in vivo and can be recultured in vitro. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 3805-3809. PMID: 16484368, PMCID: PMC1533780, DOI: 10.1073/pnas.0511218103.Peer-Reviewed Original ResearchConceptsHepatitis C virusC virusCell culture-grown hepatitis C virusChronic liver diseaseHuman liver graftsHCV culture systemsHCV life cycleLong-term infectionLiver graftsLiver diseaseCurrent therapiesHepatocellular carcinomaCell culturesInfectious virusImproved infectivityMajor causeViral infectivityVivo cultureHCVccVirusInfectious cloneVivo dissectionInfectivityCulture systemCirrhosis
2005
Unravelling hepatitis C virus replication from genome to function
Lindenbach BD, Rice CM. Unravelling hepatitis C virus replication from genome to function. Nature 2005, 436: 933-938. PMID: 16107832, DOI: 10.1038/nature04077.Peer-Reviewed Original Research
1999
Genetic Interaction of Flavivirus Nonstructural Proteins NS1 and NS4A as a Determinant of Replicase Function
Lindenbach B, Rice C. Genetic Interaction of Flavivirus Nonstructural Proteins NS1 and NS4A as a Determinant of Replicase Function. Journal Of Virology 1999, 73: 4611-4621. PMID: 10233920, PMCID: PMC112502, DOI: 10.1128/jvi.73.6.4611-4621.1999.Peer-Reviewed Original ResearchConceptsNonstructural protein 1Genetic interactionsRNA replicationViral RNA replicationGenetic screenSuppressor mutantsExtracytoplasmic compartmentsReplicase functionCytoplasmic complexDeletion mutantsReplicase componentsSingle mutationYellow fever virusProtein 1Additional mutationsNS1 geneRelated virusesInfected cellsIndependent selectionNS4A genesMutantsMutationsGenesReplicationDengue virus
1998
Noncytopathic Sindbis virus RNA vectors for heterologous gene expression
Agapov E, Frolov I, Lindenbach B, Prágai B, Schlesinger S, Rice C. Noncytopathic Sindbis virus RNA vectors for heterologous gene expression. Proceedings Of The National Academy Of Sciences Of The United States Of America 1998, 95: 12989-12994. PMID: 9789028, PMCID: PMC23682, DOI: 10.1073/pnas.95.22.12989.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBeta-GalactosidaseCell LineCloning, MolecularCricetinaeDNA-Directed RNA PolymerasesElectroporationGenes, ReporterGenetic VectorsGreen Fluorescent ProteinsKidneyLuminescent ProteinsPlasmidsRecombinant ProteinsRepliconRNA, ViralSindbis VirusTranscription, GeneticTransfectionViral ProteinsConceptsForeign gene expressionGene expressionLong-term foreign gene expressionSindbis vectorsHeterologous gene expressionDefective interfering genomesVirus-encoded genesHost protein synthesisVertebrate cellsHeterologous genesRecombinant Sindbis virusForeign genesDrug puromycinCellular metabolismProtein synthesisDNA transfectionRNA vectorSubgenomic transcriptsForeign proteinsRapid expressionBHK cellsGenesRepliconSindbis virusDramatic inhibition
1997
trans-Complementation of yellow fever virus NS1 reveals a role in early RNA replication
Lindenbach B, Rice C. trans-Complementation of yellow fever virus NS1 reveals a role in early RNA replication. Journal Of Virology 1997, 71: 9608-9617. PMID: 9371625, PMCID: PMC230269, DOI: 10.1128/jvi.71.12.9608-9617.1997.Peer-Reviewed Original Research