Walther Mothes, PhD
DownloadHi-Res Photo
Cards
Appointments
Microbial Pathogenesis
Primary
Contact Info
Microbial Pathogenesis
Department of Microbial Pathogenesis, 295 Congress Avenue
New Haven, CT 06519
United States
About
Titles
Paul B. Beeson Professor of Medicine and Professor of Microbial Pathogenesis
Biography
Dr. Mothes studied chemistry (Diploma 1993) and received a Ph.D. in cell biology (Humboldt-University Berlin, 1998) for his studies on protein secretion and membrane protein integration at the endoplasmic reticulum under the mentorship of Dr. Tom Rapoport at Harvard Medical School. He worked as a postdoctoral fellow with Dr. John Young and James Cunningham on retroviral entry before he started his own laboratory at Yale University in 2001. Dr. Mothes received Tenure in 2011, was promoted to Full Professor in 2016, and became the Paul B. Beeson Professor of Medicine in 2021.
Appointments
Microbial Pathogenesis
ProfessorPrimary
Other Departments & Organizations
- Cancer Immunology
- Center for Infection and Immunity
- HPV Working Group (Niccolai Lab)
- Microbial Pathogenesis
- Microbiology
- Molecular Virology
- Mothes Lab
- Red College Affiliates
- Virology Laboratories
- Yale Cancer Center
- Yale Combined Program in the Biological and Biomedical Sciences (BBS)
- Yale Ventures
- Yale-UPR Integrated HIV Basic and Clinical Sciences Initiative
Education & Training
- PhD
- Humboldt University of Berlin (1998)
- BC
- Humboldt University of Berlin (1993)
Research
Overview
Medical Subject Headings (MeSH)
Biophysics; HIV; Immune System; Retroviridae; SARS-CoV-2
ORCID
0000-0002-3367-7240
Research at a Glance
Yale Co-Authors
Frequent collaborators of Walther Mothes's published research.
Publications Timeline
A big-picture view of Walther Mothes's research output by year.
Research Interests
Research topics Walther Mothes is interested in exploring.
Pradeep Uchil, PhD
Priti Kumar, PhD
Irfan Ullah, PhD
Wenwei Li
Ziwei Yang
Brett Lindenbach, PhD
45Publications
4,233Citations
SARS-CoV-2
Retroviridae
Publications
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 ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsDirect-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 formulationEpistatic pathways can drive HIV-1 escape from integrase strand transfer inhibitors
Hikichi Y, Grover J, Schäfer A, Mothes W, Freed E. Epistatic pathways can drive HIV-1 escape from integrase strand transfer inhibitors. Science Advances 2024, 10: eadn0042. PMID: 38427738, PMCID: PMC10906922, DOI: 10.1126/sciadv.adn0042.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsIntegrase strand transfer inhibitorsClasses of antiretroviralsHuman immunodeficiency virusStrand transfer inhibitorsHIV-1Env mutationsTransfer inhibitorsIntegrase strand transfer inhibitor dolutegravirHIV-1 escapeResistance to dolutegravirResistance to antiretroviralsAbsence of resistance mutationsClasses of drugsCell-cell transferVirological failureImmunodeficiency virusResistance mutationsGene mutationsEnvelope glycoproteinAntiretroviralsEnvResistance mechanismsDolutegravirMutationsIntegraseViral spike-receptor interactions monitored by cryo-electron tomograpy on membranes
Mothes W, Li W, Grunst M, Qin Z, Nand E. Viral spike-receptor interactions monitored by cryo-electron tomograpy on membranes. Biophysical Journal 2024, 123: 24a. DOI: 10.1016/j.bpj.2023.11.251.Peer-Reviewed Original ResearchBioluminescence 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 ResearchCitationsAltmetricConceptsDirect-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 2Bioorthogonal click labeling of an amber-free HIV-1 provirus for in-virus single molecule imaging
Ao Y, Grover J, Gifford L, Han Y, Zhong G, Katte R, Li W, Bhattacharjee R, Zhang B, Sauve S, Qin W, Ghimire D, Haque M, Arthos J, Moradi M, Mothes W, Lemke E, Kwong P, Melikyan G, Lu M. Bioorthogonal click labeling of an amber-free HIV-1 provirus for in-virus single molecule imaging. Cell Chemical Biology 2024, 31: 487-501.e7. PMID: 38232732, PMCID: PMC10960674, DOI: 10.1016/j.chembiol.2023.12.017.Peer-Reviewed Original ResearchAltmetricConceptsHIV-1Human immunodeficiency virus-1HIV-1 provirusMinimally invasive approachImmunodeficiency virus-1HIV-1 systemInvasive approachImmune evasionEnvVirus 1Virus entryStudies of virus entryCell entrySingle-molecule Forster resonance energy transferStructural dynamicsSingle molecule imagingMultiple conformational statesForster resonance energy transferCellsClick chemistryVirion internalizationResonance energy transferMolecule imagingEnergy transferLabeling of proteins
2023
Plasma Human Immunodeficiency Virus 1 Soluble Glycoprotein 120 Association With Correlates of Immune Dysfunction and Inflammation in Antiretroviral Therapy–Treated Individuals With Undetectable Viremia
Benlarbi M, Richard J, Bourassa C, Tolbert W, Chartrand-Lefebvre C, Gendron-Lepage G, Sylla M, El-Far M, Messier-Peet M, Guertin C, Turcotte I, Fromentin R, Verly M, Prévost J, Clark A, Mothes W, Kaufmann D, Maldarelli F, Chomont N, Bégin P, Tremblay C, Baril J, Trottier B, Trottier S, Duerr R, Pazgier M, Durand M, Finzi A. Plasma Human Immunodeficiency Virus 1 Soluble Glycoprotein 120 Association With Correlates of Immune Dysfunction and Inflammation in Antiretroviral Therapy–Treated Individuals With Undetectable Viremia. The Journal Of Infectious Diseases 2023, 229: 763-774. PMID: 38035854, PMCID: PMC10938206, DOI: 10.1093/infdis/jiad503.Peer-Reviewed Original ResearchCitationsAltmetricConceptsImmune dysfunctionAntiretroviral therapyUndetectable viremiaChronic inflammationAtherosclerotic plaquesSubclinical coronary artery diseaseSub-clinical cardiovascular diseaseCoronary artery diseasePro-inflammatory cytokinesCross-sectional assessmentCanadian HIVCD4 depletionCD4 countCD8 ratioDetectable viremiaArtery diseaseIL-6Soluble gp120Cardiovascular diseaseGp120 subunitImmunomodulatory propertiesAging CohortInflammationViremiaSgp120HIV-1 Env trimers asymmetrically engage CD4 receptors in membranes
Li W, Qin Z, Nand E, Grunst M, Grover J, Bess J, Lifson J, Zwick M, Tagare H, Uchil P, Mothes W. HIV-1 Env trimers asymmetrically engage CD4 receptors in membranes. Nature 2023, 623: 1026-1033. PMID: 37993716, PMCID: PMC10686830, DOI: 10.1038/s41586-023-06762-6.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsHIV-1 Env trimersCD4 moleculeHuman immunodeficiency virus-1 (HIV-1) infectionEnv trimersAntibody-mediated immune responsesEnv-CD4 interactionVirus-1 infectionVaccine immunogen designViral envelope glycoproteinsHIV-1Immune responseCD4 receptorImmunogen designEnvelope glycoproteinVirus-like particlesCD4EnvHost cell membraneImmunogenicity and Pre-Clinical Efficacy of an OMV-Based SARS-CoV-2 Vaccine
Grandi A, Tomasi M, Ullah I, Bertelli C, Vanzo T, Accordini S, Gagliardi A, Zanella I, Benedet M, Corbellari R, Di Lascio G, Tamburini S, Caproni E, Croia L, Ravà M, Fumagalli V, Di Lucia P, Marotta D, Sala E, Iannacone M, Kumar P, Mothes W, Uchil P, Cherepanov P, Bolognesi M, Pizzato M, Grandi G. Immunogenicity and Pre-Clinical Efficacy of an OMV-Based SARS-CoV-2 Vaccine. Vaccines 2023, 11: 1546. PMID: 37896949, PMCID: PMC10610814, DOI: 10.3390/vaccines11101546.Peer-Reviewed Original ResearchCitationsAltmetricConceptsSARS-CoV-2 vaccinesSARS-CoV-2Outer membrane vesiclesImmune responseSARS-CoV-2 elicitsSARS-CoV-2 variantsPotent immune responsesEffective immune responsePre-clinical efficacyDiverse SARS-CoV-2 variantsInherent adjuvanticityVaccinated miceIntranasal challengeVaccine dosesNeutralization titresEffective vaccineVirus infectionVaccination campaignHeterologous antigensVaccineVirus replicationSpike proteinInfectivity assaysTitresPotential needAntiviral HIV-1 SERINC restriction factors disrupt virus membrane asymmetry
Leonhardt S, Purdy M, Grover J, Yang Z, Poulos S, McIntire W, Tatham E, Erramilli S, Nosol K, Lai K, Ding S, Lu M, Uchil P, Finzi A, Rein A, Kossiakoff A, Mothes W, Yeager M. Antiviral HIV-1 SERINC restriction factors disrupt virus membrane asymmetry. Nature Communications 2023, 14: 4368. PMID: 37474505, PMCID: PMC10359404, DOI: 10.1038/s41467-023-39262-2.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsPLSCR1 is a cell-autonomous defence factor against SARS-CoV-2 infection
Xu D, Jiang W, Wu L, Gaudet R, Park E, Su M, Cheppali S, Cheemarla N, Kumar P, Uchil P, Grover J, Foxman E, Brown C, Stansfeld P, Bewersdorf J, Mothes W, Karatekin E, Wilen C, MacMicking J. PLSCR1 is a cell-autonomous defence factor against SARS-CoV-2 infection. Nature 2023, 619: 819-827. PMID: 37438530, PMCID: PMC10371867, DOI: 10.1038/s41586-023-06322-y.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsC-terminal β-barrel domainSpike-mediated fusionCell-autonomous defenseLarge-scale exome sequencingΒ-barrel domainGenome-wide CRISPRSARS-CoV-2 infectionHost cell cytosolScramblase activityPhospholipid scramblaseLive SARS-CoV-2 infectionHuman lung epitheliumPLSCR1SARS-CoV-2 USASingle-molecule switchingSARS-CoV-2 variantsExome sequencingHuman populationRestriction factorsViral RNANew SARS-CoV-2 variantsSARS-CoV-2Robust activityLung epitheliumDefense factors
Academic Achievements and Community Involvement
activity HIV Research
ResearchDetails01/01/2008 - PresentGermany; France; United Kingdom +1 moreAbstract/SynopsisProfessor Mothes conducts collaborative work with German, French, British, and Singaporean researchers on HIV virology.
Links & Media
News
- November 22, 2023
How Does HIV Bind to Our T Cells? New Study Reveals the Steps
- August 18, 2021Source: Science Daily
Videos capture lethal progress of COVID-19 virus
- August 18, 2021Source: Yale News
Videos capture lethal progress of COVID-19 virus
- April 09, 2020
At Dean's Virtual Workshop, Yale Scientists Describe Their Work to Halt COVID-19 Pandemic
Related Links
Get In Touch
Contacts
Academic Office Number
Mailing Address
Microbial Pathogenesis
Department of Microbial Pathogenesis, 295 Congress Avenue
New Haven, CT 06519
United States