Figure 4. Proposed model to advance drug discovery in Chagas disease using artificial intelligence (computer-calculated compounds targeting all molecules of T. cruzi mammalian stages).

The clinically relevant forms T. cruzi trypomastigote (left cell) and intracellular amastigote (right cell) targeted for drug discovery are depicted in the picture.

Selected verified but challenging therapeutic protein targets that would inhibit T. cruzi trypomastigotes and intracellular amastigotes are depicted by lines ending in circles. For each T. cruzi protein, pointed by lines ending in circles, AI calculates compounds targeting all selected molecules of T. cruzi, and will screen millions of compounds to predict those that bind and potentially inhibit protein function. This approach has the potential to deliver drug-like compounds that will go on to further optimization and then potential drug development. Consequently, the pill, colored in red and yellow, contains selected specific drugs that bind specifically to T. cruzi proteins, are novel targets for intervention, but do not bind to the host, are effective in vitro at low nM and in in vivo at low concentrations with no or minimal side effects in infections caused by drug-resistant T. cruzi strains and with predicted excellent PK/PD for entering clinical trials. Numbers in the interphase represent algorithms, as process or set of rules to be followed in drug calculations that target T. cruzi specific proteins by AI.