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Inhibitors of dihydroorotate dehydrogenase cooperate with molnupiravir and N4-hydroxycytidine to suppress SARS-CoV-2 replication

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dc.contributor.authorStegmann, Kim M.
dc.contributor.authorDickmanns, Antje
dc.contributor.authorHeinen, Natalie
dc.contributor.authorBlaurock, Claudia
dc.contributor.authorKarrasch, Tim
dc.contributor.authorBreithaupt, Angele
dc.contributor.authorKlopfleisch, Robert
dc.contributor.authorUhlig, Nadja
dc.contributor.authorEberlein, Valentina
dc.contributor.authorIssmail, Leila
dc.contributor.authorHerrmann, Simon T.
dc.contributor.authorSchreieck, Amelie
dc.contributor.authorPeelen, Evelyn
dc.contributor.authorKohlhof, Hella
dc.contributor.authorSadeghi, Balal
dc.contributor.authorRiek, Alexander
dc.contributor.authorSpeakman, John R.
dc.contributor.authorGroß, Uwe
dc.contributor.authorGörlich, Dirk
dc.contributor.authorVitt, Daniel
dc.contributor.authorMüller, Thorsten
dc.contributor.authorGrunwald, Thomas
dc.contributor.authorPfaender, Stephanie
dc.contributor.authorBalkema-Buschmann, Anne
dc.contributor.authorDobbelstein, Matthias
dc.contributor.institutionUniversity of Aberdeen.Biological Sciencesen
dc.contributor.institutionUniversity of Aberdeen.Environment and Food Securityen
dc.contributor.institutionUniversity of Aberdeen.Energetics Research Groupen
dc.date.accessioned2023-06-13T08:35:01Z
dc.date.available2023-06-13T08:35:01Z
dc.date.issued2022-05-20
dc.descriptionFunding Information: We thank Thorsten Wolff, Daniel Bourquain, Jessica Schulz, and Christian Mache from the Robert-Koch Institute and Martin Beer from the Friedrich Loeffler Institute (FLI) for providing isolates of SARS-CoV-2 variants. We thank Anna Kraft and Gabriele Czerwinski (both FLI) for support in the preparation of samples for pathology, and Catherine Hambly (University of Aberdeen) for help with daily energy expenditure measurements. We would like to thank Cathrin Bierwirth (University Medical Center Göttingen), Isabell Schulz, Anne-Kathrin Donner, and Frank-Thorben Peters for excellent technician assistance and Jasmin Fertey and Alexandra Rockstroh for providing the virus stocks for the mice experiment (Fraunhofer Institute IZI Leipzig). We acknowledge support by the Open Access Publication Funds of the Göttingen University. KMS was a member of the Göttingen Graduate School GGNB during this work. This work was funded by the COVID-19 Forschungsnetzwerk Niedersachsen (COFONI) to MD, by the Federal Ministry of Education and Research Germany ( Bundesministerium für Bildung und Forschung; BMBF ; OrganSARS , 01KI2058 ) to SP and TM, and by a grant of the Max Planck Foundation to DG. Declaration of interests AS, HK, EP, and DV are employees of Immunic AG and own shares and/or stock-options of the parent company of Immunic AG, Immunic Inc. Some of the Immunic AG employees also hold patents for the Immunic compounds described in this manuscript (WO2012/001,148, WO03006425). KMS, AD, and MD are employees of University Medical Center Göttingen, which has signed a License Agreement with Immunic AG covering the combination of DHODH inhibitors and nucleoside analogs to treat viral infections, including COVID-19 (inventors: MD, KMS, and AD). The other authors declare no conflict of interest.en
dc.description.statusPeer revieweden
dc.format.extent27
dc.format.extent6259756
dc.identifier237156617
dc.identifier87b0e8fe-cc76-4dde-8fd2-15b42491bef6
dc.identifier85129931016
dc.identifier.citationStegmann, K M, Dickmanns, A, Heinen, N, Blaurock, C, Karrasch, T, Breithaupt, A, Klopfleisch, R, Uhlig, N, Eberlein, V, Issmail, L, Herrmann, S T, Schreieck, A, Peelen, E, Kohlhof, H, Sadeghi, B, Riek, A, Speakman, J R, Groß, U, Görlich, D, Vitt, D, Müller, T, Grunwald, T, Pfaender, S, Balkema-Buschmann, A & Dobbelstein, M 2022, 'Inhibitors of dihydroorotate dehydrogenase cooperate with molnupiravir and N4-hydroxycytidine to suppress SARS-CoV-2 replication', iScience, vol. 25, no. 5, 104293. https://doi.org/10.1016/j.isci.2022.104293en
dc.identifier.doi10.1016/j.isci.2022.104293
dc.identifier.iss5en
dc.identifier.urihttps://hdl.handle.net/2164/20828
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85129931016&partnerID=8YFLogxKen
dc.identifier.vol25en
dc.language.isoeng
dc.relation.ispartofiScienceen
dc.subjectDrugsen
dc.subjectVirologyen
dc.subjectRM Therapeutics. Pharmacologyen
dc.subjectGeneralen
dc.subject.lccRMen
dc.titleInhibitors of dihydroorotate dehydrogenase cooperate with molnupiravir and N4-hydroxycytidine to suppress SARS-CoV-2 replicationen
dc.typeJournal articleen

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