Machine Learning-Guided Repositioning of a SARS-CoV-2-Targeting Molecular Series as Cruzain Inhibitors.

ABSTRACT: Drug repurposing and repositioning are concepts that involve identifying alternative therapeutic uses for existing drug candidates or molecular series. During the COVID-19 pandemic, hundreds of antivirals were developed, many of which remain unexplored for other diseases. Concurrently, machine learning (ML) has become a valuable tool in early drug discovery for screening the most promising compounds for a target. In this work, an ExtraTrees ML model is developed to predict inhibitory activity against cruzain, the main cysteine protease of Trypanosoma cruzi, the causative agent of Chagas disease. The model is used to screen a proprietary library of peptidomimetic compounds originally designed to target SARS-CoV-2 M^pro and human cathepsin L. High-affinity cruzain inhibitors are id

SUBMITTER: Lameiro RF 

PROVIDER: S-EPMC12860495 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature