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

Author:

Sala SamueleORCID,Nitschke PhilippORCID,Masuda ReikaORCID,Gray NicolaORCID,Lawler NathanORCID,Wood James M.,Buckler Joshua N.,Berezhnoy Georgy,Bolaños Alejandro,Boughton Berin A.ORCID,Lonati Caterina,Rössler Titus,Singh Yogesh,Wilson Ian D.,Lodge SamanthaORCID,Morillon Aude-Claire,Loo Ruey LengORCID,Hall DrewORCID,Whiley LukeORCID,Evans Gary B.,Grove Tyler L.,Almo Steven C.ORCID,Harris Lawrence D.ORCID,Holmes ElaineORCID,Merle Uta,Trautwein ChristophORCID,Nicholson Jeremy K.ORCID,Wist JulienORCID

Abstract

AbstractWe present compelling evidence for the existence of an extended innate viperin dependent pathway which provides crucial evidence for an adaptive response to viral agents like SARS-CoV-2. We show the in vivo biosynthesis of a family of endogenous cytosine metabolites with potential antiviral activity. 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 allowed the characterization and quantification of the most abundant serum metabolites showing 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. 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 defence mechanism against viral infection.

Publisher

Cold Spring Harbor Laboratory

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