Looking around the world and around the corner in COVID-19 research

In the midst of COVID-19, we ignore global collaboration and creative innovation at our peril.

The novel coronavirus pandemic is forcing researchers to look far and wide for effective pathways, policies and antivirals against the disease.

A race against time

The race against COVID has revealed the dire consequences when governments fail to adopt a more globally collaborative and evidence-based strategy.

For instance, the United States’ insistence on self-reliance may have cost them valuable testing potential. While coronavirus tests were delayed by contamination in Center for Disease Control (CDC) labs in the US, the World Health Organization (WHO) was shipping hundreds of thousands of tests to other nations worldwide.

Moreover, the CDC refused to follow the test-design protocol laid out by the WHO, and burdensome regulations from the Food and Drug Administration (FDA) stymied private companies from developing their own tests.

While the rest of Europe imposed strict lockdown protocols, Sweden chose a more relaxed approach. While the lasting economic and health impacts of this choice are still in the making, Sweden’s chief scientist behind their strategy has since called their death toll “horrifying”.

Around the world, bureaucratic inflexibility and lack of cooperation have contributed to the rapid spread of this unprecedented disease.

But our shortcomings against COVID span far broader than government initiatives. In clinical research as in legislation, global collaboration and flexibility will prove essential to rise to this Herculean task.

A fresh approach to scientific innovation

COVID has forced researchers to look at alternative approaches to help contain the disease.

Desperation has bred creativity. Antiviral drugs that had been approved or investigated for Ebola, influenza and more have since been appropriated for clinical testing against COVID. Some, like former hepatitis C drug remdesivir, have shown promise in clinical trials.

Energy and inflammation in COVID research

One unique area of research that seems to hold unexpected promise involves cellular energy and metabolism. Researchers are unfurling the complex relationship between regulation of inflammation and the cellular energy molecule NAD+.

Scientists have found the inflammatory response to COVID operates best within a ‘Goldilocks zone’: too much inflammation leads to a ‘cytokine storm’ and the fatal acute respiratory distress syndrome (ARDS) seen in many coronavirus patients; too little allows the virus to spread unperturbed.

Your infected cells walk this tightrope by upregulating protective enzymes like sirtuins and polyadenosine diphosphate-ribose polymerases (PARPs), which have been shown to play a role in innate immune response. However, all these cellular defence processes are highly energetically expensive, depleting infected cells of NAD+.

COVID has been shown to deplete NAD+ levels by as much as 80% — in fact, studies of infected human lungs suggest the virus may even try to suppress cells from producing new NAD+^1,2. In one type of essential immune cell called a macrophage, NAD+ depletion has been linked to immune dysfunction³.

California nutraceutical company ChromaDex is committed to conducting COVID-19 research following promising initial preclinical findings showing viral infections deplete NAD+ and SARS-CoV-2 infected cells activate the NAD+ defence pathway that utilises nicotinamide riboside (NR).

In preclinical models (like cells and mice), NR has been shown to activate sirtuins and decrease hyper-inflammatory cytokine release, like those contributing to the deadly lung complication ARDS.

NR has been proven in eight clinical trials to safely and effectively boost NAD+ with no known attributable side-effects. NR is approved for sale in the United States, Canada, the European Union and Australia.

In legislation as well as in science, people are learning the hard way to think outside the box and follow the evidence where it leads.

References

1. Blanco-Melo, D et al., SARS-CoV-2 launches a unique transcriptional signature from in vitro, ex vivo, and in vivo systems. bioRxiv, 2020: p. 2020.03.24.004655.
2. Heer, CD et al., Coronavirus Infection and PARP Expression Dysregulate the NAD Metabolome: A Potentially Actionable Component of Innate Immunity. bioRxiv, 2020: p. 2020.04.17.047480.
3. Minhas, PS et al., Macrophage de novo NAD(+) synthesis specifies immune function in aging and inflammation. Nat Immunol, 2018.

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