The preclinical study results were published July 8 on scientific publishing website bioRxiv.org.
The research conducted jointly at the University of Iowa, Oregon Health and Science University, and the University of Kansas previously demonstrated in a preclinical cell model that levels of the coenzyme NAD+ were depleted up to 80% in Coronavirus-infected cells.
Consistent with those findings, the new study showed that the loss of NAD+ appeared to disrupt genes involved with cell defense which can impair cells' innate immune response.
The researchers hypothesized that if NAD+ depletion worsened cells' defenses and aided viral replication, raising NAD+ levels with nicotinamide riboside (NR, or Niagen) may have an anti-viral effect.
These latest results confirmed their hypothesis by demonstrating that cell lines infected with a type of Coronavirus had decreased viral replication when supplemented with NR.
The collaborative research team also found that the activity of antiviral PARP enzymes was upregulated by boosting NAD pharmacologically.
The team of investigators used a multi-pronged approach involving a form of Coronavirus and performed experiments in multiple separate cell models.
Following infection, they measured various NAD metabolites, expression of genes encoding enzymes involved in NAD biosynthesis, expression of genes encoding NAD-dependent enzymes critical for host cell defense and viral replication rates.
While many of the underlying mechanisms are yet to be elucidated, the team found that several NAD-dependent termed PARPs are activated following SARS-CoV-2 infection.
Cellular defenses may become overwhelmed as the cell and the virus play "tug of war" over NAD, resulting in severe NAD shortages needed to block viral replication.
Additional research is necessary to explore the role NAD may play in maintaining a proportional inflammatory response to infection, and whether a depletion of NAD may worsen the "cytokine storm" that results in the fatal acute respiratory distress syndrome seen in some COVID patients.
Dr. Brenner and the team of scientists are continuing their investigations into the antiviral potential of Niagen in order to translate the findings from the lab to the clinic. Ultimately, clinical trials are required to determine whether Niagen impacts COVID-19 infection in humans.
Through the ChromaDex External Research Program, ChromaDex has also expedited research materials and data to members of the scientific community seeking to understand the potential role of Niagen in COVID-19. This research was also supported by the National Institutes of Health, the Roy J. Carver Trust, and the Pew Charitable Trusts.
Brenner first discovered NR's NAD-boosting potential in 2004 and has been the Roy J. Carver chair and Head of Biochemistry at the University of Iowa since 2009.
This summer, Brenner's laboratory will relocate to city of Hope National Medical Center in California, where he will continue his research as the Alfred E. Mann chair of the new Department of Diabetes and Cancer Metabolism.
ChromaDex, the exclusive licensee of Dr. Brenner's patented NR, has since invested over USD 35m in investigating, manufacturing and offering NR in the form of Niagen and has secured more than 20 patents.
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