Khushi Kethana

Optimizing small-molecule inhibition of sJIA and MAS biomarker IL-18 receptor IL-18Ra via Autodock and Osprey 3.0

Started June 25, 2021

Abstract or project description

Systemic juvenile idiopathic arthritis (sJIA) is a subtype of juvenile idiopathic arthritis (JIA) characterized by systemic inflammation of joints and sometimes organs. SJIA has no known cause, but there are known biomarkers, of which one is high concentrations of interleukin-18 (IL-18), a proinflammatory cytokine involved in regulating the transcription of other proinflammatory cytokines. In sJIA, the “free” concentration is elevated, especially in patients with a past history of macrophage activation syndrome (MAS), a condition sJIA patients are prone to in which there is an overproduction of T lymphocytes and corresponding overproduction of inflammatory cytokines. As a result, IL-18 receptor antagonism serves as a potential treatment for sJIA patients non-responsive to previous treatment and patients who have experienced MAS. In this project, potential inhibitors of IL-18Ra will be docked and optimized using Autodock Vina and Osprey 3.0, respectively. The results of the binding and optimizing will be compared and will aid in developing drug therapy for sJIA and MAS patients.