SARS-CoV-2 Infection Biomarkers Reveal an Extended RSAD2 Dependant Metabolic Pathway

Samuele Sala; Philipp Nitschke; Reika Masuda; Nicola Gray; Nathan Lawler; James Wood; Georgy Berezhnoy; Alejandro Bolanos; Berin Boughton; Caterina Lonati; Titus Roessler; Yogesh Singh; Ian Wilson; Samantha Lodge; Aude-Claire Morillon; Ruey Loo; Drew Hall; Luke Whiley; Gary Evans; Tyler Grove; Steven Almo; Lawrence Harris; Elaine Holmes; Uta Merle; Christoph Trautwein; Jeremy Nicholson; Julien Wist

doi:10.1101/2023.05.08.23289637

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SARS-CoV-2 Infection Biomarkers Reveal an Extended RSAD2 Dependant Metabolic Pathway

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SARS-CoV-2 Infection Biomarkers Reveal an Extended RSAD2 Dependant Metabolic Pathway

Samuele Sala, Philipp Nitschke, Reika Masuda, Nicola Gray, Nathan Lawler, James Wood, Georgy Berezhnoy, Alejandro Bolanos, Berin Boughton, Caterina Lonati, …

MedRxiv

Cold Spring Harbor Laboratory Press

2023

DOI: https://doi.org/10.1101/2023.05.08.23289637

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Abstract

Antiviral activity

Immune system

Interleukin 10

Metabolic pathways

NMR

Nuclear magnetic resonance

Nucleoside analogs

Severe acute respiratory syndrome coronavirus 2

Spectroscopy

γ-Interferon

We present compelling evidence for the existence of an evolutionary adaptive response to viral agents such as SARS-CoV-2, that results in the human in vivo biosynthesis of a family of compounds with potential antiviral activity. Using nuclear magnetic resonance (NMR) spectroscopy, we detected a characteristic spin-system motif indicative of the presence of an extended panel of urinary and serum metabolites during the acute viral phase. The structure of eight of nucleoside analogues was elucidated (six of which have not previously been reported in human urine), and subsequently confirmed by total-synthesis and matrix spiking. 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 endogenous innate immune defense mechanism against viral infection.

Details

Title: SARS-CoV-2 Infection Biomarkers Reveal an Extended RSAD2 Dependant Metabolic Pathway
Authors/Creators: Samuele Sala - Murdoch University
Philipp Nitschke - Murdoch University
Reika Masuda - Murdoch University
Nicola Gray - Murdoch University
Nathan Lawler - Murdoch University
James Wood - Victoria University of Wellington
Georgy Berezhnoy - Siemens (Germany)
Alejandro Bolanos - Universidad del Valle
Berin Boughton - Murdoch University
Caterina Lonati - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Titus Roessler - Siemens (Germany)
Yogesh Singh
Ian Wilson - Imperial College London
Samantha Lodge - Murdoch University
Aude-Claire Morillon - Murdoch University
Ruey Loo - Murdoch University
Drew Hall - Murdoch University
Luke Whiley - Murdoch University
Gary Evans - Victoria University of Wellington
Tyler Grove - Albert Einstein College of Medicine
Steven Almo - Albert Einstein College of Medicine
Lawrence Harris - Victoria University of Wellington
Elaine Holmes - Murdoch University
Uta Merle - University Hospital Heidelberg
Christoph Trautwein - Siemens (Germany)
Jeremy Nicholson - Murdoch University
Julien Wist - Murdoch University
Publication Details: MedRxiv
Publisher: Cold Spring Harbor Laboratory Press; Cold Spring Harbor
Identifiers: 991005600060507891
Murdoch Affiliation: Health Futures Institute; Centre for Computational and Systems Medicine
Language: English
Resource Type: Preprint

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