After the COVID-19 pandemic, many of us are acutely aware of how viral infections can decimate our bodies. Severe influenza A virus (IAV), much like the virus responsible for COVID, can cause hyper-inflammation in the lungs and eventual acute respiratory distress, for which we currently do not have an effective treatment for. However, we know that a protein in our bodies called receptor interacting protein kinase 3 (RIPK3) is activated by the virus during infection, leading to lung and airway inflammation and cell death. Therefore, one potential way we could reduce acute respiratory distress caused by IAV is by finding a compound that could inhibit, or deactivate, this protein.

Recently, researchers came across a compound that could inhibit a protein similar to RIPK3. They then made variations of that compound, changing the chemical structure slightly with each iteration, to get a version that would specifically inhibit only RIPK3. Eventually, they discovered a candidate compound that deactivated RIPK3 not only in a test tube but also in mouse models. They also showed in their mouse models that this drug could significantly reduce lung inflammation and even prevent death from a severe IAV infection.

While drugs tested in mouse models often fail human clinical trials, successful experiments in mice as shown here is the first step towards developing a treatment for acute respiratory distress caused by IAV. RIPK3 is also involved in a variety of diseases including asthma, inflammatory bowel disease, and even cancer so a compound that could inhibit its function could be beneficial for a wide group of patients. Although the work is still in its infancy, the findings in this paper are quite promising, and perhaps one day, we could all breathe a deep sigh of relief with the approval of this compound for human use.

This study was led by researchers at the Center for Immunology at the Fox Chase Cancer Center and the Department of Immunology at St Jude Children’s Research Hospital, under the guidance of corresponding authors Gregory D. Cuny, Paul G. Thomas, Alexei Degterev and Siddharth Balachandran.

Managing Correspondent: Jenny Kim

Press Article: Fox Chase Cancer Center Study Demonstrates Promise of New Therapy for Lung Injury From Severe Flu Infection (Fox Chase Cancer Center)

Original Journal Article: Necroptosis blockade prevents lung injury in severe influenza (Nature)

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