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 formulationBioluminescence imaging reveals enhanced SARS-CoV-2 clearance in mice with combinatorial regimens
Ullah I, Escudie F, Scandale I, Gilani Z, Gendron-Lepage G, Gaudette F, Mowbray C, Fraisse L, Bazin R, Finzi A, Mothes W, Kumar P, Chatelain E, Uchil P. Bioluminescence imaging reveals enhanced SARS-CoV-2 clearance in mice with combinatorial regimens. IScience 2024, 27: 109049. PMID: 38361624, PMCID: PMC10867665, DOI: 10.1016/j.isci.2024.109049.Peer-Reviewed Original ResearchDirect-acting antiviralsEfficacy of direct-acting antiviralsVirus clearanceSARS-CoV-2Bioluminescence imagingSuppressed viral loadK18-hACE2 miceRapid virus clearanceNeutralizing antibody treatmentSARS-CoV-2 clearanceEvaluate therapeutic efficacyCOVID-19 convalescent plasmaMonotherapy regimensCombinatorial regimensAntibody treatmentViral loadSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Lung pathologyPandemic potentialRespiratory syndrome coronavirus 2Therapeutic arsenalConvalescent plasmaTreatment efficacySyndrome coronavirus 2