Diseño computacional de nuevos fármacos más potentes y especifico para el tratamiento de micosis severas de relevancia epidemiológica

The present project aims to design more powerful and specific drugs for the treatment of mycosis caused by histoplasma capsulatum and candida albicans, combining bioinformatic and experimental methodologies. histoplasmosis (hpm) is the most frequent systemic mycosis in america, caused by the dimorphic fungus histoplama capsulatum, which is acquired by the host through the inhalation route. in colombia, we do not have real epidemiological data, as it is not a notifiable disease, however, it is presumed that there may currently be ~ 10 million asymptomatic people who are infected with this fungus, but under conditions such as an hiv coinfection. (70%) or treatment with immunosuppressants and biological products, which weaken the host's immune system,they can suffer a significant increase in the burden of the disease, which is already observed in our population. specific treatment for hpm is indicated in all immunocompromised patients and in those with acute or chronic lung disease, progressive disseminated and in patients with occasional pulmonary and mediastinal complications. in the most severe cases of this mycosis, the administration of amphotericin b is recommended, which, although it has a broad spectrum of coverage and a potent fungicidal effect, has the adverse effects of an important renal toxicity and reactions to the infusion. on the other hand, for the milder clinical form of the disease, itraconazole is administered, which has good activity against the fungus, but triggers many drug interactions. further,the treatment lasts between 12 weeks and 24 months, which significantly increases not only the cost, but also the potential side effects.

Validar posibles blancos terapéuticos en la vía de señalización del fosfatidilinositol en hongos, y diseñar fármacos más potentes y específicos para el tratamiento de micosis severas de relevancia epidemiológica, combinando herramientas bioinformáticas y experimentales.

' en el presente proyecto se explorará por primera vez la opción de utilizar proteínas de la vía de señalización del fosfatidilinositol como dianas moleculares en hongos. ' realizaremos un amplio estudio bioinformático, para varios tipos de hongos, con el objetivo de identificar posibles sitios de unión a drogas (no solo el sitio activo) en las enzimas de la vía de señalización del fosfatidilinositol, comparándolos con los correspondientes sitios en las proteínas humanas homólogas, y produciendo así un mapa de posibles sitios específicos y "drogables" en estos microorganismos.