New Research Suggests Oxaloacetate Supplementation as an Antiviral Defense

Just published in the journal “Nature Microbiology” the article, “Oxaloacetate sensing promotes innate immune antiviral defence against influenza virus infection.” 

The article uncovers a new function of oxaloacetate supplementation—to promote the defense against viruses. The research examined increased cellular oxaloacetate levels via supplementation as a strategy to reduce infection and increase survival against viral infections.

“OAA supplementation provides a broad-spectrum antiviral ability, and OAA deficiency caused by Acly genetic ablation decreases antiviral immunity and renders mice more susceptible to lethal H1N1 virus infection. Our results uncover a signalling pathway through cellular OAA sensing that links metabolism and innate immunity to coordinate defence against viral challenge.”

The antiviral effect was broad, with oxaloacetate supplementation reducing titers of

• Influenza virus A/Puerto Rico/8/34 (PR8, N1N1)H1N1,
• Influenza virus A/California/04/09 (CA04, H1N1),
• HSV-1-3GFP,
• HSV-1, ZIKV GZ01 (KU820898),
• 1AV and
• Dengue virus (strain 16681) in human cell lines. 

Although COVID-19 was not tested, an antiviral response to potential residual COVID virus may provide yet another mechanism to help explain oxaloacetate’s positive treatment against Long-COVID in recent clinical trials. 

In order to boost oxaloacetate concentrations in the cell, researchers used the diethyl-ester form (DEOAA), which would be a drug candidate for further exploration. The DEOAA put more OAA in the cells, but OAA supplementation alone was also effective against influenza.

“OAA supplementation recovered the enhanced IAV infection with MEDICA16 treatment (Fig. 1a), and OAA treatment displayed a dose-dependent inhibitory effect on IAV infection (Fig. 1b–d). Similar phenomena were observed in A549 and THP-1 cells infected with IAV PR8 and CA04 strains (Fig. 1e,f).

While this work was done on human cell cultures and the survival studies were performed in mice, and not confirmed in human clinical trials, it does suggest that further research be mobilized to examine how oxaloacetate may provide benefits against the common cold and other viral infections. Shortages of oxaloacetate lead to increased lethal infections in the mice models from H1N1.