Sodium Pyruvate Ameliorates Influenza A Virus Infection In Vivo

Abstract

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 h 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 an 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 day 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.

Inhalation of Sodium Pyruvate to Reduce the Symptoms and Severity of Respiratory Diseases Including COVID-19, Long COVID, and Pulmonary Fibrosis

“…Seventeen other clinical trials with data submitted to the U.S. FDA also demonstrate similar findings in patients treated with N115 including COPD, cystic fibrosis, allergic rhinitis, sinusitis and influenza infected patients where lung function, NO and SaO2 improved with N115 treatment. In this study, as in the previous 17 studies, N115 must be inhaled, and our previous work shows that the route of administration is important for the function of sodium pyruvate (13,14). Overall, our results demonstrate that N115 is a promising treatment that warrants further investigation.…”

“…Previously, we demonstrated that treatment with sodium pyruvate can improve inflammation and decrease viral loads in mice during infection with influenza A virus and HSV1 [13,14]. As pyruvate acts on the host immune response, through metabolic pathways and not directly on the virus [15], our data demonstrate that sodium pyruvate is a promising treatment option that is safe, effective, and unlikely to elicit antiviral resistance.…”

“…N115 treated patients did have slightly higher fever and took longer for chills, body aches and headaches to return to normal. As N115 works by modulating the immune response, including increasing NO etc., and not by direct antiviral activity, some increase in immune responses is anticipated while others are anticipated to decrease [13][14][15]. However, saline, does not affect in- flammation or inflammatory cytokines, does not decrease oxygen radicals, or decrease coughing or increase lung functions, which are all desirable for treatment of COVID-19 and Long COVID or patients with PF and are documented with N115.…”

“…Mortality was similar between groups, but the infectious dose was not expected to result in high mortality. From this preliminary animal study, and in conjunction with multitudes of previously reported safety data [13,14], we proceeded with a clinical trial in humans with active infection of SARS CoV-2.…”

Sodium Pyruvate Nasal Spray Reduces the Severity of Nasal Inflammation and Congestion in Patients with Allergic Rhinitis

“… 10 Furthermore, the inhalation of sodium pyruvate in mice produced statistically significant reductions in IL-6 and IL-1β over the inhalation of saline. 11 …”