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 formulation
2021
Modulating HIV-1 envelope glycoprotein conformation to decrease the HIV-1 reservoir
Rajashekar JK, Richard J, Beloor J, Prévost J, Anand SP, Beaudoin-Bussières G, Shan L, Herndler-Brandstetter D, Gendron-Lepage G, Medjahed H, Bourassa C, Gaudette F, Ullah I, Symmes K, Peric A, Lindemuth E, Bibollet-Ruche F, Park J, Chen HC, Kaufmann DE, Hahn BH, Sodroski J, Pazgier M, Flavell RA, Smith AB, Finzi A, Kumar P. Modulating HIV-1 envelope glycoprotein conformation to decrease the HIV-1 reservoir. Cell Host & Microbe 2021, 29: 904-916.e6. PMID: 34019804, PMCID: PMC8214472, DOI: 10.1016/j.chom.2021.04.014.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, NeutralizingAntibody-Dependent Cell CytotoxicityAntiviral AgentsCD4 AntigensCD4-Positive T-LymphocytesCell LineEnv Gene Products, Human Immunodeficiency VirusEpitopesFemaleGlycoproteinsHEK293 CellsHIV InfectionsHIV-1HumansImmunoglobulin Fc FragmentsKiller Cells, NaturalMaleMiceMice, SCIDModels, AnimalProtein ConformationVirus ReplicationConceptsAntibody-dependent cellular cytotoxicityHIV-1 reservoirFc effector functionsViral reboundHumanized miceHIV-1HIV-1-infected individualsHIV-1-infected cellsAutologous HIV-1Natural killer cellsCD4-mimetic compoundsHIV-1 replicationSmall CD4-mimetic compoundsART interruptionFunctional cureNK cellsKiller cellsCellular cytotoxicityTherapeutic utilityInfected individualsCD4mcVirus reservoirMiceViral envelopeAntibody recognition