Recently, an in-tandem approach made up of computational studies and surface plasmon resonance (SPR) turned out to be useful for the identification of new putative CF drugs and for the comprehension of their mechanism of action. Here researchers propose to: 1) exploit drug repositioning for the identification of novel drugs endowed with F508del CFTR-rescuing capacity; 2) characterize the molecular interactions and mechanisms of action of the repurposed drugs by means of a multidisciplinary approach including computational analysis and SPR, with the aim to finely characterize their binding modes and mechanism of action on F508del-CFTR; 3) validate the therapeutic potential of the repositioned drugs by means of appropriate cell-based assays for CF. New structural models of the intact human F508del-CFTR embedded in a lipid environment will be used in a drug repositioning framework to select from AIFA, FDA and natural compounds databases a set of repositioned drugs able to bind to F508del-CFTR. Repositioned drugs will be evaluated for their capacity to effectively rescue F508del-CFTR in appropriate biochemical analysis (thermostability assay) and cell-based models (including primary cultures of human bronchial epithelial cells derived from CF patients).