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
2022
Molecular basis for antiviral activity of two pediatric neutralizing antibodies targeting SARS-CoV-2 Spike RBD
Chen Y, Prévost J, Ullah I, Romero H, Lisi V, Tolbert W, Grover J, Ding S, Gong S, Beaudoin-Bussières G, Gasser R, Benlarbi M, Vézina D, Anand S, Chatterjee D, Goyette G, Grunst M, Yang Z, Bo Y, Zhou F, Béland K, Bai X, Zeher A, Huang R, Nguyen D, Sherburn R, Wu D, Piszczek G, Paré B, Matthies D, Xia D, Richard J, Kumar P, Mothes W, Côté M, Uchil P, Lavallée V, Smith M, Pazgier M, Haddad E, Finzi A. Molecular basis for antiviral activity of two pediatric neutralizing antibodies targeting SARS-CoV-2 Spike RBD. IScience 2022, 26: 105783. PMID: 36514310, PMCID: PMC9733284, DOI: 10.1016/j.isci.2022.105783.Peer-Reviewed Original ResearchReceptor-binding domainSARS-CoV-2 patientsK18-hACE2 micePlasma neutralization activitySARS-CoV-2 variantsSARS-CoV-2 spike receptor-binding domainSpike receptor-binding domainProphylactic administrationNAb responsesPediatric patientsPotent NAbsLethal challengeNeutralizing antibodiesNeutralization activityDelta VOCEffector activityAntiviral mechanismAntiviral activityClinical interventionsPatientsNAbsAntibodiesEpitopesMolecular determinantsMolecular basis
2015
Broad CTL response is required to clear latent HIV-1 due to dominance of escape mutations
Deng K, Pertea M, Rongvaux A, Wang L, Durand CM, Ghiaur G, Lai J, McHugh HL, Hao H, Zhang H, Margolick JB, Gurer C, Murphy AJ, Valenzuela DM, Yancopoulos GD, Deeks SG, Strowig T, Kumar P, Siliciano JD, Salzberg SL, Flavell RA, Shan L, Siliciano RF. Broad CTL response is required to clear latent HIV-1 due to dominance of escape mutations. Nature 2015, 517: 381-385. PMID: 25561180, PMCID: PMC4406054, DOI: 10.1038/nature14053.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsAnti-HIV AgentsCD4-Positive T-LymphocytesChronic DiseaseEpitopes, T-LymphocyteFemaleGag Gene Products, Human Immunodeficiency VirusGenes, DominantGenes, ViralHIV InfectionsHIV-1HumansMaleMiceMutationRNA, ViralT-Lymphocytes, CytotoxicViral LoadVirus LatencyVirus Replication