Christina Wangen

The murine correlate of the Epstein-Barr and Kaposi’s sarcoma-associated γ-herpesviruses, MHV-68, represents a valuable model to assess antiviral drug sensitivity and combinatorial drug synergies

Christina Wangen, Debora Obergfäll, Katarína Briestenská, J Mistríková et autres

Human herpesviruses represent major human pathogens. Members of the γ-Herpesvirinae subfamily are of particular interest because they cause chronic diseases, such as cancers, by altering cellular processes and driving resting cells into a continuously proliferating phase. Also, autoimmune diseases such as multiple …

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Assessment of combined antiviral drug treatment against selected α-, β-, and γ-herpesviruses

Lucio Fortelny, Christina Wangen, Debora Obergfäll, Kishore Dhotre et autres

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DHODH Inhibitors Based on the Vidofludimus Scaffold Containing Carboxylic Acid Bioisosteres Exert a Superior Broad-Spectrum Antiviral Activity

Alexandra Herrmann, Friedrich Hahn, Christina Wangen, Sabrina Wagner et autres

Emerging and re-emerging viral infections demand the rapid development of broad-spectrum antivirals. Host-directed therapies targeting cellular metabolic pathways required for viral replication offer a promising strategy with a low risk of resistance. Dihydroorotate dehydrogenase (DHODH), the rate-limiting enzyme in de novo pyrimidine …

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Identification of a New Phosphorylated Host Interactor of the Epstein–Barr Virus (EBV) Kinase BGLF4 Suggests Key Points for EBV-Specific Antiviral Drug Targeting

Melanie Kögler, Christina Wangen, Alena Hammerschmitt, Debora Obergfäll et autres

Epstein–Barr virus (EBV) is a human pathogenic and oncogenic herpesvirus, with worldwide importance, at times associated with serious to life-threatening symptoms, especially in immunocompromised hosts. The available preventive options against EBV disease are limited to medically elaborate and cost-intensive measures of cell-based …

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The murine homolog of Epstein-Barr virus, MHV-68, represents a highly valuable model to assess antiviral drug sensitivity and combinatorial drug synergies

Christina Wangen, Debora Obergfäll, Katarína Briestenská, J Mistríková et autres

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The phospho-dynamics of cytomegalovirus capsid interaction, with its protein kinase and nuclear egress complex, provide an antiviral targeting concept

Julia Tillmanns, Christina Wangen, Sigrun Häge, T. Rovis et autres

Human cytomegalovirus (HCMV) is a major pathogen with worldwide distribution. Improved insight into antiviral targeting is urgently needed for drug development. Viral nuclear capsid egress is a validated target for new small molecules, including the approved viral kinase inhibitor maribavir (MBV). A …

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Conserved mode of nuclear lamina distortion by primate cytomegaloviruses: importance of the pSer22 motif, viral kinase and cis/trans isomerase Pin1 activity

Kishore Dhotre, Martin Schütz, Lucio Fortelny, Christina Wangen et autres

Human cytomegalovirus (HCMV) is a ubiquitous human pathogen of high clinical relevance. In terms of pathogenic determination, the regulatory factors of HCMV–host interaction play a crucial role, and recently we reported on virus-supportive functions of the cellular peptidyl-prolyl cis / trans isomerase …

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New Assay Systems to Characterize the Broad-Spectrum Antiherpesviral and Non-Herpesviral Activity of Cyclin-Dependent Kinase (CDK) 8 Inhibitors

Debora Obergfäll, Friedrich Hahn, Jintawee Kicuntod, Christina Wangen et autres

Background. To date, a number of human pathogenic viruses are still unaddressed by the current repertoire of approved antiviral drugs. In order to widen this spectrum of preventive measures against virus infections, we have focused on additional host targets that exert interesting …

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Facile Synthesis of New Antiviral Fluoro-Quinazolines Enabled by Merging Domino Reactions

Svetlana B. Tsogoeva, Sascha Kohlbauer, Honglin Xia, Benedikt W. Grau et autres

Abstract Quinazolines, particularly fluoro-quinazolines, represent important structural motifs in bioactive molecules and pharmaceuticals. Despite several known synthetic routes, the efficient synthesis of fluorine-containing quinazolines remains a challenge. Herein, the straightforward and sustainable synthesis of fluorine-substituted quinazolines using domino sequences is reported. The …

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Cyclin-Dependent Kinase 8 Represents a Positive Regulator of Cytomegalovirus Replication and a Novel Host Target for Antiviral Strategies

Debora Obergfäll, Markus Wild, Mona Sommerer, Malena Barillas Dahm et autres

Background. Cyclin-dependent kinase 8 (CDK8) is a multifaceted regulator and represents a catalytic component of the transcriptional Mediator complex. CDK8 activity, on the one hand, increases transcriptional elongation by the recruitment of Mediator/super elongation complexes, but, on the other hand, negatively regulates …

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Orally bioavailable RORγ/DHODH dual host-targeting small molecules with broad-spectrum antiviral activity

Alexandra Herrmann, Christian Gege, Christina Wangen, Sabrina Wagner et autres

Host-directed antivirals (HDAs) represent an attractive treatment option and a strategy for pandemic preparedness, especially due to their potential broad-spectrum antiviral activity and high barrier to resistance development. Particularly, dual-targeting HDAs offer a promising approach for antiviral therapy by simultaneously disrupting multiple …

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Understanding the Cytomegalovirus Cyclin-Dependent Kinase Ortholog pUL97 as a Multifaceted Regulator and an Antiviral Drug Target

Manfred Marschall, Martin Schütz, Markus Wild, Eileen Socher et autres

Herpesviral protein kinases, such as the therapy-relevant pUL97 of human cytomegalovirus (HCMV), are important for viral replication efficiency as well as pathogenesis, and represent key antiviral drug targets. HCMV pUL97 is a viral cyclin-dependent kinase (CDK) ortholog, as it shares functional and …

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