SCREENING FOR IRF5 INHIBITORS

Abstract: Interferon regulatory factor 5 (IRF5) is a protein with different functions including theactivation of genes that encode different cytokines. Overexpression of IRF5 has been observedto lead to different types of stress in the cells, including an overproduction of cytokines, whichis referred to as a cytokine storm. Clinical states in which dysregulated cytokine release in theform of a cytokine storm can be referred to with an umbrella term: Cytokine storm syndrome.The aim of this study was to test for inhibitors for IRF5 that could be developed and used as apharmaceutical drug to treat Cytokine Storm Syndromes including autoimmune diseases andCOVID-19. The method for this screeing consisted of finding possible inhibitors usingcomputer based drug design which resulted in the selection of 21 possible inhibitors. Thesesubstances were then tested on induced macrophages that are cytokine producing. The abilityfor inhibition is based on the amount of cytokines present in the sample after exposure. Thiswas tested using an ELISA based assay which measures the amount of cytokines in the sample..A handful of substances was found to be effective and substances 11 and 17 stood out asespecially effective. This indicates the possibitily for a drug to be developed that would inhibitIRF5, which could be used for treatment of cytokine storm syndromes.Keywords: IRF5,