Preclinical research from Dr. Charles Brenner and a team of leading scientists from three US universities concludes that key steps in coronavirus infection and innate immunity involve a tug-of-war with cellular NAD, according to press materials.
ChromaDex Corp the innovators behind Niagen® (patented nicotinamide riboside) science, announced the publication of results from preclinical research on cells and animal tissue infected with Coronavirus and a COVID-19 cadaver in the online scientific publishing website bioRxiv.org investigating the effect of viral infection on levels of NAD within the cell (note the COVID-19 studies on bioRvix are not peer-reviewed so as to present at much information as possible during the pandemic).
The data showed a COVID-19 assault on the cells causes a greater than three-fold reduction in NAD and triggers the infected cells to specifically seek out nicotinamide riboside (NR) in an attempt to replenish NAD levels in the face of viral infection. While further research is underway, this early preclinical data suggests that increasing cytoplasmic NAD levels through a NAD precursor, such as NR, may support innate immunity to coronaviruses and other viruses.
“The virus and infected cells appear to be playing a tug-of-war with cellular NAD,” reports lead investigator Dr. Charles Brenner. “Infected cells activate a set of genes to use NAD for defense while the virus has a specific gene to try to defeat this. These infected cells also have a gene expression program that provides insight into how we may be able to strengthen innate immunity.”
This new research conducted jointly at the University of Iowa, Oregon Health & Science University, and the University of Kansas determined that coronaviruses, including SARS-CoV-2, the causative agent of COVID-19, greatly disturb the NAD system. Cells, animals and a person infected with SARS-CoV-2 turn on three to eight different so-called PARP genes that use NAD as part of an apparent innate immune response. The researchers showed that coronavirus infection depletes cellular NAD and that PARP gene expression depresses NAD. The gene expression program of infected ferrets also indicated that infected cells specifically seek out NR to replenish NAD levels in the face of viral infection.
Dr. Brenner added, “we began a collaboration years ago at University of Iowa with Drs. Anthony Fehr and Stanley Perlman with observations that coronaviruses potentially target cellular NAD. Now working with Dr. Fehr’s group at University of Kansas and Dr. Michael Cohen’s group at Oregon Health & Science University and with the support of five different institutes at the National Institutes of Health, the Pew Charitable Trusts, and the Roy J. Carver Charitable Trust, we’ve been able to show that not only does the virus attack cellular NAD, but also that approaches to protect NAD are likely to differ in their effectiveness. By looking at the gene expression program of ferrets infected with SARS-CoV-2 and from the lung tissue of a person who died of COVID-19, we can see that some NAD synthesis pathways are down and others including the NR pathway are up. We’re excited to continue to uncover how infected cells use NAD for their immune defenses and are looking forward to testing NR in animal models of coronavirus infection.”
Dr. Brenner is the Roy J. Carver Chair & Head of Biochemistry of the University of Iowa, and Chief Scientific Advisor to ChromaDex. Dr. Brenner is one of the world’s foremost experts in NAD research, having discovered the unique NAD-boosting properties of NR in 2004.
Published research has demonstrated decreased NAD levels to be associated with a variety of physiological stresses in humans and animal models. Stress from viral infections is also known to deplete NAD and adversely affect cell resilience.
“As a science-based company with a unique NAD boosting molecule and knowing that our cells’ NAD is depleted by viral infections, we take our responsibility seriously and will leverage our science resources to expedite continuing research on the potential impact of Niagen,” says Rob Fried, ChromaDex CEO.
Dr. Andrew Shao, ChromaDex Senior Vice President of Global Scientific & Regulatory Affairs, adds, “We know from clinical research that increased NAD levels help protect our cells from a variety of physiological stresses. We are pleased to support researchers from around the world exploring the effects of NR to help restore cellular health and aid cellular defense and repair to maintain NAD.”
In an effort to advance research on COVID-19, ChromaDex is expediting research materials and data to members of the scientific community including participants of the ChromaDex External Research Program (CERP) who are studying its patented molecule in relation to COVID-19.