Leishmania and Trypanosoma are protozoan parasites causing vector-borne zoonosis that affect millions of people worldwide. These infections constitute a serious health issue in low-income countries but are endemic in developed countries as well, including the Mediterranean basin. Vaccines are lacking and current treatments are unsatisfactory due to toxicity, poor efficacy and resistance, thus new drugs are urgently needed.
This project aims at contributing to the development of an effective broad-spectrum trypanocidal drug through a rational structure-based approach focused on two promising protein targets, trypanothione reductase (TR) and ornithine decarboxylase (ODC), essential for proliferation and redox homeostasis of Trypanosomatidae. Structural and functional characterization of the targets will be carried out by state-of-the-art techniques, aiding the structure-based design of potent drug-like compounds and supporting the future work of research groups interested in trypanocidal drug development. In addition, we will explore a delivery strategy based on the encapsulation of eflornithine in the protein ferritin, with the double aim to validate ODC as a target and ferritin as a drug carrier for leishmaniasis.
The modular organization of the project, comprised of parallel work packages for the proposed targets, maximizes the probability of success, preventing the failure of one or more steps from compromising the entire research plan.
