Coronavirus and PARP expression dysregulate the NAD Metabolome: a potentially actionable component of innate immunity.

BioRxiv : the Preprint Server for Biology
C. D. HeerCharles Brenner


SARS-CoV-2 is a coronavirus (CoV) and cause of COVID-19, which is much more lethal in older people and those with comorbid conditions for unknown reasons. Innate immune responses to CoVs are initiated by recognition of double-stranded RNA and induction of interferon, which turns on a gene expression program that inhibits viral replication. Here we show that SARS-CoV-2 infection of cells, ferrets and a person strikingly dysregulates the NAD gene set by inducing a set of PARP family members that includes enzymes required for the innate immune response to CoVs. CoV infection also induces a severe attack on host cell NAD. Overexpression of one induced enzyme, PARP10, is sufficient to depress host NAD. Gene expression and pharmacological data suggest that boosting NAD through the nicotinamide and nicotinamide riboside kinase pathways may restore antiviral PARP functions to support innate immunity to CoVs, whereas PARP1,2 inhibition does not restore PARP10 activity.


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bronchoalveolar lavage
chemical treatments
restriction digest

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