NAD+Coronavirus infection dysregulate the NAD Metabolome

User avatar
AlbertY
Posts: 146
Joined: Mon Aug 12, 2019 4:01 pm
Location: Boston, MA

Coronavirus infection dysregulate the NAD Metabolome

Post by AlbertY » Sun Jul 12, 2020 2:31 pm

Here is a new study by Charles Brenner.

In short, Coronavirus infection will deplete cellular NAD, and NR supplementation ameliorate that.
Here we show that SARS-CoV-2 infection strikingly dysregulates the set of genes involved in consumption and biosynthesis of nicotinamide adenine dinucleotide (NAD). Highly induced genes include those encoding noncanonical poly(ADP-ribose) polymerase (PARP) family members known to function as mono ADP-ribosyltransferases but not known to deplete cellular NAD and genes encoding enzymes for salvage NAD synthesis from nicotinamide (NAM) and nicotinamide riboside (NR). We demonstrate that overexpression of PARP10 is sufficient to depress NAD levels and that the enzymatic activities of PARP10, PARP12 and PARP14 are limited by and can be enhanced by pharmacological activation of NAM salvage. We further showed that infection with the β-coronavirus murine hepatitis virus (MHV) induces a severe attack on host cell NAD+ and NADP+. Finally we show that NAMPT activation, NAM and NR dramatically decrease replication in a MHV infection model that is sensitive to PARP activity. The data show that the antiviral activities of noncanonical PARP isozyme activities are limited by their own consumption of cellular NAD and that nutritional and pharmacological interventions to enhance NAD-based defenses may boost innate immunity.
https://www.biorxiv.org/content/10.1101 ... 7.047480v5


Ph.D. student at Harvard Medical School, doing research on aging