Viral pneumonia, influenza conceptual illustration

In a stride towards combating influenza, scientists from the Tufts University School of Medicine, in collaboration with other scientific institutions, have introduced a promising compound, UH15-38, showing the potential to significantly relieve lung damage and inflammation caused by the flu virus.

Influenza, a pervasive and often severe respiratory illness, can lead to serious complications, particularly among the elderly, young children, and individuals with preexisting health conditions. The body’s response to the flu virus involves a complex interplay of mechanisms, one of which is necroptosis—a form of cell death that, while initially serving as a crucial alert system, can lead to severe tissue damage if not properly regulated.

Reporting in Nature, the study focused on the compound UH15-38, which has been shown to inhibit necroptosis by targeting and blocking a specific pathway known as receptor interacting protein kinase 3 (RIPK3). By preventing the overactivation of this pathway, UH15-38 significantly reduced lung inflammation and injury, offering a beacon of hope for patients suffering from severe influenza infections.

The collaborative effort behind this research involved key contributions from multiple institutions, including Fox Chase Cancer Center, the University of Houston, and St. Jude Children’s Research Hospital.

Alexei Degterev, an associate professor at the Tufts University School of Medicine and co-corresponding author of the study, explained, “Necroptosis does not appear to be necessary for restricting viral activity, so if we can block it, we will be able to protect the host by reducing inflammation in the lungs.”

Remarkably, UH15-38 demonstrated a high tolerance in mice, with no intolerable side effects observed. The compound proved effective even when administered up to five days into the infection, preventing any influenza-induced fatalities in the study’s animal models.

According to the scientists, this finding suggests that UH15-38 could serve as a vital tool in treating severe flu infections, potentially extending its benefits to other viruses that cause severe respiratory symptoms.

As the world continues to grapple with the aftermath of the COVID-19 pandemic, the threat of future pandemics looms large. In this context, Degterev’s work is particularly important.

“While the worst of COVID-19 may be behind us, the credible expectation is that there will be another pandemic. We need something that is going to protect the host independent of how the host is infected,” he emphasized in a press statement.

The development and testing of UH15-38 are ongoing, with Tufts University’s Office for Technology Transfer and Industry Collaboration overseeing its commercialization. The researchers are also exploring second-generation inhibitors that could offer even greater efficacy and safety.

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