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?:abstract
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Influenza A virus (IAV) causes seasonal epidemics annually and pandemics every few decades. Most antiviral treatments used for IAV are only effective if administered during the first 48 hours of infection and antiviral resistance is possible. Therapies that can be initiated later during IAV infection and that are less likely to elicit resistance will significantly improve treatment options. Pyruvate, a key metabolite, and end product of glycolysis, has been studied for many uses, including its anti-inflammatory capabilities. Sodium pyruvate was recently shown by us to decrease inflammasome activation during IAV infection. Here, we investigated sodium pyruvate’s effects on IAV in vivo. We found that nebulizing mice with sodium pyruvate decreased morbidity and weight loss during infection. Additionally, treated mice consumed more chow during infection indicating improved symptoms. There were notable improvements in pro-inflammatory cytokine production (IL-1β) and lower virus titers on days 7 post-infection in mice treated with sodium pyruvate compared to control animals. As pyruvate acts on the host immune response and metabolic pathways and not directly on the virus, our data demonstrate that sodium pyruvate is a promising treatment option that is safe, effective, and unlikely to elicit antiviral resistance.
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