Setting New Routes for Antifungal Drug Discovery Against Pathogenic Fungi.

Fungal diseases are life-threatening to human health and cause an important burden around the world, being associated with high numbers of morbidity and mortality. The current antifungal treatment comprises drugs such as azoles, echinocandins and polyenes but most of the time the cure is not guaranteed, it has severe side effects and can last for a long period of time. Thus, setting new routes for the discovery of effective and safe antifungal drugs should be priority within the health care system. The discovery of new, alternative efficient and antifungal drugs with fewer side effects is very slow and remains a challenge. Natural products can be a source of antifungals and used in combinatorial therapy. Plants produce metabolites that can inhibit pathogen growth and these compounds have been intensely explored. Several proteins, enzymes and metabolic pathways could be targets for the discovery of efficient inhibitor compounds and recently, heat shock proteins, calcineurin, salinomycin, trehalose biosynthetic pathway and the glyoxylate cycle have been investigated in several fungal species. Transcriptomic and proteomic approaches have advanced antifungal drug discovery and pointed to new important specific-pathogen targets. Finally, computation biology has helped in the search of more effective approaches and early antifungal drug discovery, since it takes several years from discovery to clinical use. Thus, the development of new antifungal strategies might reduce the therapeutic time and increase the quality of life of patients.