Computational approach for calpain inhibitors discovery with potential antiparasitic activity against Leishmania Infantum. From MS label-free proteomic analysis to hits identification through virtual screening.

 The aim of this STSM is the validation of the selected target (calpain) and the identification of novel compounds that will be tested for their antiparasitic potential (Leishmania spp.). Along with computational bioinformatic approaches, MS proteomic analysis is a powerful way to find biological pathways and, by extension, proteins that are involved in certain conditions to find new druggable targets. These approaches can also help in finding molecules that can overcome drug resistance in parasitic diseases. Based on these assumptions, our group has investigated how this new target could be used to do structure-based virtual screening (SBVS) to find new hit compounds that might be able to treat leishmaniasis. Currently, the lack of an x-ray crystal structure of calpain requires the construction of a homology model of the protein. Validation of the model will then be performed, and the active site will be analyzed and employed for a structure-based virtual screening. Finally, the newly identified compounds will be obtained (purchased or synthesized) and tested in vitro against Leishmania spp. The goal is to identify potential drug candidates that can inhibit calpain and potentially serve as new 

treatments for leishmaniasis. Once the compounds are tested in vitro, further studies will be conducted to evaluate their efficacy, selectivity, and safety.