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Journal article
Integrative Molecular Structure Elucidation and Construction of an Extended Metabolic Pathway Associated with an Ancient Innate Immune Response in COVID-19 Patients
Journal of proteome research, Vol.23(3), pp.956-970
2024
PMID: 38310443
Abstract
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.
Details
- Title
- Integrative Molecular Structure Elucidation and Construction of an Extended Metabolic Pathway Associated with an Ancient Innate Immune Response in COVID-19 Patients
- Authors/Creators
- Samuele Sala - The Australian National Phenome Centre and Computational and Systems Medicine, Health Futures Institute, Murdoch University, Harry Perkins Building, Perth WA6150, AustraliaPhilipp Nitschke - The Australian National Phenome Centre and Computational and Systems Medicine, Health Futures Institute, Murdoch University, Harry Perkins Building, Perth WA6150, AustraliaReika Masuda - The Australian National Phenome Centre and Computational and Systems Medicine, Health Futures Institute, Murdoch University, Harry Perkins Building, Perth WA6150, AustraliaNicola Gray Dr - The Australian National Phenome Centre and Computational and Systems Medicine, Health Futures Institute, Murdoch University, Harry Perkins Building, Perth WA6150, AustraliaNathan G Lawler - The Australian National Phenome Centre and Computational and Systems Medicine, Health Futures Institute, Murdoch University, Harry Perkins Building, Perth WA6150, AustraliaJames Wood - Ferrier Research Institute, Victoria University of Wellington, Wellington 6012, New Zealand, The Maurice Wilkins Centre for Molecular Biodiscovef Wellington, Welry, The University of Auckland, Auckland 1010, New ZealandJoshua N. Buckler - Ferrier Research Institute, Victoria University of Wellington, Wellington 6012, New ZealandGeorgy Berezhnoy - Department of Preclinical Imaging and Radiopharmacy, Werner Siemens Imaging Center, University Hospital Tübingen, 72074 Tübingen, GermanyJose Bolaños - Chemistry Department, Universidad del Valle, Cali 76001, ColombiaBerin Boughton A. - The Australian National Phenome Centre and Computational and Systems Medicine, Health Futures Institute, Murdoch University, Harry Perkins Building, Perth WA6150, AustraliaCaterina Lonati - Center for Preclinical Research, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, ItalyTitus Rössler - Department of Preclinical Imaging and Radiopharmacy, Werner Siemens Imaging Center, University Hospital Tübingen, 72074 Tübingen, GermanyYogesh Singh - Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, 72074 Tübingen, GermanyIan D. Wilson - Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College, Burlington Danes Building, Du Cane Road, London W12 0NN, U.KSam L LodgeAude-Claire Morillon - The Australian National Phenome Centre and Computational and Systems Medicine, Health Futures Institute, Murdoch University, Harry Perkins Building, Perth WA6150, AustraliaRuey Leng Leng Loo - The Australian National Phenome Centre and Computational and Systems Medicine, Health Futures Institute, Murdoch University, Harry Perkins Building, Perth WA6150, AustraliaDrew Hall - The Australian National Phenome Centre and Computational and Systems Medicine, Health Futures Institute, Murdoch University, Harry Perkins Building, Perth WA6150, AustraliaLuke Whiley - The Australian National Phenome Centre and Computational and Systems Medicine, Health Futures Institute, Murdoch University, Harry Perkins Building, Perth WA6150, AustraliaGary Evans - Ferrier Research Institute, Victoria University of Wellington, Wellington 6012, New Zealand, The Maurice Wilkins Centre for Molecular Biodiscovef Wellington, Welry, The University of Auckland, Auckland 1010, New ZealandTyler Grove - Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, United StatesSteven Almo - Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, United StatesLawrence Harris D. - Ferrier Research Institute, Victoria University of Wellington, Wellington 6012, New Zealand, The Maurice Wilkins Centre for Molecular Biodiscovef Wellington, Welry, The University of Auckland, Auckland 1010, New ZealandElaine Holmes - The Australian National Phenome Centre and Computational and Systems Medicine, Health Futures Institute, Murdoch University, Harry Perkins Building, Perth WA6150, Australia, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College, Burlington Danes Building, Du Cane Road, London W12 0NN, U.KUta Merle - Department of Internal Medicine IV, University Hospital Heidelberg, 69120 Heidelberg, GermanyChristoph Trautwein - Department of Preclinical Imaging and Radiopharmacy, Werner Siemens Imaging Center, University Hospital Tübingen, 72074 Tübingen, GermanyJeremy K. Nicholson - The Australian National Phenome Centre and Computational and Systems Medicine, Health Futures Institute, Murdoch University, Harry Perkins Building, Perth WA6150, Australia, Institute of Global Health Innovation, Faculty of Medicine, Imperial College London, Level 1, Faculty Building, South Kensington Campus, London SW7 2NA, U.KJulien Wist - The Australian National Phenome Centre and Computational and Systems Medicine, Health Futures Institute, Murdoch University, Harry Perkins Building, Perth WA6150, Australia, Chemistry Department, Universidad del Valle, Cali 76001, Colombia, Faculty of Medicine, Department of Metabolism, Digestion and Reproduction, Division of Digestive Diseases at Imperial College, London SW7 2AZ, U.K
- Publication Details
- Journal of proteome research, Vol.23(3), pp.956-970
- Publisher
- American Chemical Society
- Identifiers
- 991005638069907891
- Copyright
- © 2024 The Authors.
- Murdoch Affiliation
- Centre for Computational and Systems Medicine; Health Futures Institute
- Language
- English
- Resource Type
- Journal article
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