St. Jude Reference #SJ-21-0008
COVID-19, a pandemic contagious disease caused by the recently identified coronavirus SARS-CoV-2, is characterized by excessive production of pro-inflammatory cytokines and acute lung damage associated with extensive cell death. Although initial cytokine cascades may be beneficial to the host for clearing the virus, enhanced production of pro-inflammatory cytokines and increasing levels in the systemic circulation, referred to as cytokine storm, can promote tissue damage by inducing cell death in both infected and bystander cells. While multiple inflammatory cytokines are produced during SARS-CoV-2 infection, researchers at St. Jude found that the combination of TNF and IFN- g specifically induced multiple cell death mechanisms, collectively termed PANoptosis. They further found that blocking the TNF and IFN- g signaling pathway inhibits PANoptosis and may benefit patients with COVID-19 or other conditions that trigger a cytokine storm.
Approved drugs that inhibit TNF and IFN-γ activity, as well as those that target other molecules in the pathway (e.g., JAK), are currently available and could potentially be repurposed to inhibit the cytokine storm associated with various conditions, including COVID-19, sepsis, hemophagocytic lymphohistiocytosis, and cytokine shock syndromes.
TNF alpha inhibitors are used to treat Crohn’s disease, ulcerative colitis, and rheumatoid and psoriatic arthritis. Approved TNF inhibitors are: infliximab, adalimumab, certolizumab, golimumab, etanercept, thalidomide, lenalidomide, pomalidomide, pentoxifylline, bupropion, or delmitide.
Approved INF- g inhibitors are: emapalumab, fontolizumab, AMG 811, vidofludimus, or delmitide.
COVID-19, SARS-CoV-2, pro-inflammatory cytokines, sepsis, hemophagocytic lymphohistiocytosis, cytokine shock syndrome, acute lung damage associated with extensive cell death, cytokine storm, combination of TNF and IFN- g, PANoptosis,
Granted Patents or Published Applications
A provisional application is pending
Related Scientific References
"COVID-19 cytokines and the hyperactive immune response: Synergism of TNF-α and IFN-γ in triggering inflammation, tissue damage, and death." Cell, Published November 18, 2020. DOI: https://doi.org/10.1016/j.cell.2020.11.025
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