Coronavirus Infection and PARP Expression Dysregulate the NAD Metabolome: A Potentially Actionable Component of Innate Immunity

Collin D. Heer, Daniel J. Sanderson, Yousef M.O. Alhammad, Mark S. Schmidt, Samuel A.J. Trammell, Stanley Perlman, Michael S. Cohen, Anthony R. Fehr, Charles Brenner

Posted: April 30, 2020 - This version is a preprint and has not been certified by peer review.
This article shows that SARS-CoV-2 infection of cell lines, infected ferrets, and a deceased patient’s lung consistently and strikingly dysregulates NAD+ (nicotinamide adenine dinucleotide) gene set with respect to NAD+ synthesis and utilization. Further, it shows that MHV infection induces an attack on host cell NAD+ and NADP+ (nicotinamide adenine dinucleotide phosphate)


  • “…viral replication and host cell homeostasis both depend on the four nicotinamide adenine dinucleotide (NAD) coenzymes, NAD+, NADH, NADP+ and NADPH, which are the central catalysts of metabolism (Belenky, Bogan, & Brenner, 2007). These coenzymes accept and donate electrons in essential, ubiquitous processes of fuel oxidation, biosynthesis, and the generation and detoxification of reactive oxygen species” (emphasis added)
  • “…SARS-CoV-2 infection of ferrets and the human also appears to down-regulate synthesis of NAD from tryptophan and nicotinic acid (NA) while upregulating synthesis capacity from nicotinamide (NAM) and nicotinamide riboside (NR)…” (emphasis added)
  • “…The data justify further analysis of how nutritional and therapeutic modulation of NAD status may potentially restrict viral infection by boosting innate immunity...." (emphasis added)
  • “… NAD boosting approaches have the potential to support the innate immune system and address the age-, smoking- and comorbid conditions associated with worse SARS-CoV-2 outcomes (Yang et al., 2020). Coupled with good hygiene, the potential societal benefit of a safe and readily available molecule to support prevention and public health is hard to overstate, especially as people emerge from sheltering in place and re-enter public spaces with potentially substantive viral contamination…" (emphasis added)

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