Alexandra Herrmann

Vidofludimus calcium for the treatment of multiple sclerosis: development rationale, mechanism of action, and early trial data

Matej Ondrus, Robert J. Fox, Evelyn Peelen, Juliano Fonseca et autres

INTRODUCTION: Multiple sclerosis (MS) is an autoimmune condition of the central nervous system associated with progressive disability. Safe and well tolerated treatments targeting both inflammatory and neurodegenerative processes are needed to address the spectrum of MS pathophysiology. AREAS COVERED: Vidofludimus calcium is …

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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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The power of printed word in a digital age: Effects of a mental health brochure on help-seeking in college students

Abigail Nerogic, Erica K. Yuen, Cynthia Elizabeth Gangi, Michael J. Stasio et autres

Objective: The current study investigated how viewing a printed informational brochure about local mental health resources can affect help-seeking in college students. Method: Undergraduate participants (n = 187) were randomly assigned to read a printed brochure for 5 min about local mental …

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Molecular analysis of the 2022 mpox outbreak and antiviral activity of dihydroorotate dehydrogenase inhibitors against orthopoxviruses

Arne Cordsmeier, Alexandra Herrmann, Christian Gege, Hella Kohlhof et autres

Monkeypox virus (MPXV) has caused a large pandemic outbreak in 2022 with more than 90.000 confirmed cases and 181 deaths. Notably, signs of microevolution and host adaption have been observed. Here, we demonstrate that viral genomes from Franconia, Bavaria acquired different mutations. …

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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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Synthesis and Characterization of DHODH Inhibitors Based on the Vidofludimus Scaffold with Pronounced Anti‐SARS‐CoV‐2 Activity

Christian Gege, Friedrich Hahn, Christina Wangen, Sigrun Häge et autres

New strategies for the rapid development of broad-spectrum antiviral therapies are urgently required for emerging and re-emerging viruses like the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Host-directed antivirals that target universal cellular metabolic pathways necessary for viral replication present a promising …

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Validation of nuclear receptor RORγ isoform 1 as a novel host-directed antiviral target based on the modulation of cholesterol levels

Christina Wangen, Andrea Raithel, Julia Tillmanns, Christian Gege et autres

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ORF3c is expressed in SARS‐CoV‐2‐infected cells and inhibits innate sensing by targeting MAVS

Martin C. Müller, Alexandra Herrmann, Shigeru Fujita, Keiya Uriu et autres

Most SARS-CoV-2 proteins are translated from subgenomic RNAs (sgRNAs). While the majority of these sgRNAs are monocistronic, some viral mRNAs encode more than one protein. One example is the ORF3a sgRNA that also encodes ORF3c, an enigmatic 41-amino-acid peptide. Here, we show …

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Iota-Carrageenan Inhibits Replication of the SARS-CoV-2 Variants of Concern Omicron BA.1, BA.2 and BA.5

Christian Setz, Maximilian Große, Maria Fröba, Janina Auth et autres

Even with its endemic transition, the COVID-19 pandemic remains a public health threat, particularly in the light of emerging variants of concern (VoCs) and the need for pandemic preparedness in the future. In November 2021, the SARS-CoV-2 VoC Omicron emerged and its …

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Analysis of SARS-CoV-2 Spike Protein Variants with Recombinant Reporter Viruses Created from a Bacmid System

Arne Cordsmeier, Doris Jungnickl, Alexandra Herrmann, Klaus Korn et autres

SARS-CoV-2, the causative agent of COVID-19, has spread around the world with more than 700 million cases and 6.8 million deaths. Various variants of concern (VoC) have emerged due to mutations and recombination and concurrent selection for increased viral fitness and immune …

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ORF3c is expressed in SARS-CoV-2 infected cells and suppresses immune activation by inhibiting innate sensing

Martin C. Müller, Alexandra Herrmann, Shigeru Fujita, Keiya Uriu et autres

ABSTRACT SARS-CoV-2 proteins are translated from subgenomic RNAs (sgRNAs). While most of these sgRNAs are monocistronic, some viral mRNAs encode more than one protein. For example, the ORF3a sgRNA also encodes ORF3c, an enigmatic 4l-amino acid peptide. Here, we show that ORF3c …

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Spike and nsp6 are key determinants of SARS-CoV-2 Omicron BA.1 attenuation

Da‐Yuan Chen, Chue Vin Chin, Devin Kenney, Alexander H. Tavares et autres

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