Chagas Disease Novel Drug Targets and Treatments

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Background

Background: Chagas disease or American Trypanosomiasis, is a parasitic infection that affects millions of people all over most Latin American countries. The World Health Organization calculates that the number of infected individuals extends to 6-7 million people, estimating that 20.000 death occurs yearly. The transmission of the etiologic agent Trypanosoma cruzi (T.cruzi) through people migrating to non-endemic nations, has become a globalized public health concern.

Currently, the only available drug treatment options for the disease are nitro-heterocyclic nifurtimox (Nx) and benznidazole (Bz). Both have fluctuating efficacy, long treatment schedules, and toxicity associated with treatment. The discovery of novel molecules against Chagas disease is necessary and underway.

There are three key group targets for the development of novel drugs with trypanocidal activity. The three target groups classify as follows: Group I, contains the main molecular specific enzymes involved in the essential processes of parasite survival, such as the catalytic part of cruzipain (Cz), the main antigenic parasite cysteine proteinase (CP). Group II comprises atypical metabolic biological pathways and their key specific enzymes, such as sterol biosynthesis pathway, specific antioxidant defense mechanisms, and bioenergetic ones. Group III includes the atypical organelles, structures present in the relevant clinical forms, which are absent or different from those present in mammals and biological processes related to them.

Goal: Over the last decades, the top promising targets for trypanocidal drugs recognized have been the atypical ergosterol biosynthesis pathway and the cruzain truncated T. cruzi recombinant Cz. In addition to the metabolic pathways containing their related enzymes, the protozoan cellular biology includes nuclear, and cytoplasmatic characteristic structures. Among T.cruzi organelles, single kinetoplastic-containing-mitocondrium and acidocalcisomes, are both involved in the parasite bioenergetic. Moreover, detailed studies from several specific biosynthetic pathways have been investigated and specific enzymes from these routes have been explored. In the last years, novel atypical potential targets have been also reported.
The identification and validation of novel parasite targets can open new possibilities in the development of effective and secure therapeutic trypanocidal compounds, increasing our knowledge on T. cruzi drug targets. Distinguishing discrepancies between the host and the parasite targets will also help to combat this neglected disease through different strategies.

Therefore, the aim of this Research Topic is to report the identification of novel T. cruzi drug targets and to deepen our knowledge of currently known ones. This also includes recent advances using different approaches, in the identification of anti-T. cruzi compounds related to parasite targets; the repurposing of drugs already used in humans to target T. cruzi; and latest advances on therapy directed to target host pathways in close interaction with the parasite.

Scope: In this Research Topic we welcome submissions that cover the following sub-themes:
• Novel or advanced knowledge on known T. cruzi drug targets.
• In silico identification of T. cruzi drug targets.
• Design and synthesis of anti-T. cruzi compounds including new chemical scaffolds, focused to parasite targets.
• Promising anti-T. cruzi drugs with or without known potential specific target activity.
• Repurposing of drugs previously used in humans for other treatments to target T. cruzi.
• Recent therapy directed to target host pathways responsible for T. cruzi parasite invasion, survival, and pathogenicity.

Keywords: Chagas Disease, Trypanosoma Cruzi, Drug Targets, Metabolic Pathways, Key Enzymes, Atypical Organelles, Therapies

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