1 research outputs found
Integrative Molecular Structure Elucidation and Construction of an Extended Metabolic Pathway Associated with an Ancient Innate Immune Response in COVID-19 Patients
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