Integrating molecular similarity and alphafold-based structural alignment for target discovery in trypanosoma cruzi

by Ros-Lucas A, Martínez-Peinado N, Gabaldón-Figueira JC, Morillo-Osorio M, Ballart C, Gállego M, Pinazo M-J, Gascón J, Requena-Méndez A, Alonso-Padilla J. Pharmaceuticals 2026, 19(7):1046. doi:10.3390/ph19071046

Summary: Computational approaches offer a cost-effective and fast alternative to traditional methods for early-stage drug discovery. The authors of this study present an integrated in silico pipeline combining ligand-based and structure-based computational approaches to prioritize potential molecular targets for bioactive compounds against Trypansoma cruzi. The pipeline was validated using known targets; the correct target was recovered in six of eight cases. Two additional compounds with anti-T. cruzi activity, but unknown mechanisms of action, were analyzed to hypothesize their potential targets. The pipeline demonstrated moderate success but was limited by challenges in handling novel chemotypes and poorly annotated targets. Nevertheless, its modular nature allows for easy adaptation to other neglected tropical diseases, providing a flexible and cost-effective framework for early-stage target prioritization.

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