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
2008
Novel non-active site inhibitor of Cryptosporidium hominis TS-DHFR identified by a virtual screen
Martucci WE, Udier-Blagovic M, Atreya C, Babatunde O, Vargo MA, Jorgensen WL, Anderson KS. Novel non-active site inhibitor of Cryptosporidium hominis TS-DHFR identified by a virtual screen. Bioorganic & Medicinal Chemistry Letters 2008, 19: 418-423. PMID: 19059777, PMCID: PMC2651159, DOI: 10.1016/j.bmcl.2008.11.054.Peer-Reviewed Original ResearchConceptsThymidylate synthase-dihydrofolate reductaseHuman enzymeNovel allosteric pocketSite inhibitorsSynthase-dihydrofolate reductaseFlavin mononucleotideActive site inhibitorsVirtual screenLinker regionAllosteric pocketInhibitor targetingSpecies specificitySite pocketDrug targetsCryptosporidium hominisNovel inhibitorsEnzymeMicromolar potencySelective inhibitorNoncompetitive inhibitorInhibitorsLead compoundsScreenPocketReductase