دورية أكاديمية
Integrative Molecular Structure Elucidation and Construction of an Extended Metabolic Pathway Associated with an Ancient Innate Immune Response in COVID-19 Patients
| العنوان: | Integrative Molecular Structure Elucidation and Construction of an Extended Metabolic Pathway Associated with an Ancient Innate Immune Response in COVID-19 Patients |
|---|---|
| المؤلفون: | Samuele Sala, Philipp Nitschke, Reika Masuda, Nicola Gray, Nathan G. Lawler, James M. Wood, Joshua N. Buckler, Georgy Berezhnoy, Jose Bolaños, Berin A. Boughton, Caterina Lonati, Titus Rössler, Yogesh Singh, Ian D. Wilson, Samantha Lodge, Aude-Claire Morillon, Ruey Leng Loo, Drew Hall, Luke Whiley, Gary B. Evans, Tyler L. Grove, Steven C. Almo, Lawrence D. Harris, Elaine Holmes, Uta Merle, Christoph Trautwein, Jeremy K. Nicholson, Julien Wist |
| سنة النشر: | 2024 |
| مصطلحات موضوعية: | Biochemistry, Medicine, Genetics, Ecology, Immunology, Cancer, Infectious Diseases, Virology, Computational Biology, Chemical Sciences not elsewhere classified, viperin enzyme contributing, provides crucial evidence, present compelling evidence, potential diagnostic value, potential antiviral activities, unveiled ten nucleoside, extended innate viperin, antiviral compounds <, abundant serum metabolites, urinary metabolites, serum cytokines, nucleoside analogues, innate production, extended panel, vivo biosynthesis, viral infections, viral infection, viral agents, system motif, spectroscopy revealed |
| الوصف: | We present compelling evidence for the existence of an extended innate viperin-dependent pathway, which provides crucial evidence for an adaptive response to viral agents, such as SARS-CoV-2. We show the in vivo biosynthesis of a family of novel endogenous cytosine metabolites with potential antiviral activities. Two-dimensional nuclear magnetic resonance (NMR) spectroscopy revealed a characteristic spin-system motif, indicating the presence of an extended panel of urinary metabolites during the acute viral replication phase. Mass spectrometry additionally enabled the characterization and quantification of the most abundant serum metabolites, showing the potential diagnostic value of the compounds for viral infections. In total, we unveiled ten nucleoside (cytosine- and uracil-based) analogue structures, eight of which were previously unknown in humans allowing us to propose a new extended viperin pathway for the innate production of antiviral compounds . The molecular structures of the nucleoside analogues and their correlation with an array of serum cytokines, including IFN-α2, IFN-γ, and IL-10, suggest an association with the viperin enzyme contributing to an ancient endogenous innate immune defense mechanism against viral infection. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| العلاقة: | https://figshare.com/articles/journal_contribution/Integrative_Molecular_Structure_Elucidation_and_Construction_of_an_Extended_Metabolic_Pathway_Associated_with_an_Ancient_Innate_Immune_Response_in_COVID-19_Patients/25140695Test |
| DOI: | 10.1021/acs.jproteome.3c00654.s001 |
| الإتاحة: | https://doi.org/10.1021/acs.jproteome.3c00654.s001Test https://figshare.com/articles/journal_contribution/Integrative_Molecular_Structure_Elucidation_and_Construction_of_an_Extended_Metabolic_Pathway_Associated_with_an_Ancient_Innate_Immune_Response_in_COVID-19_Patients/25140695Test |
| حقوق: | CC BY-NC 4.0 |
| رقم الانضمام: | edsbas.4104C851 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1021/acs.jproteome.3c00654.s001 |
|---|