In silico approaches supporting drug repurposing for Leishmaniasis

Abstract

The shortage of treatment options for leishmaniasis, especially those easy to administer and viable for deployment in the world's poorest regions, highlights the importance of employing these strategies to cost-effectively investigate repurposing candidates. This scoping review aims to map the studies using in silico methodologies for drug repurposing against leishmaniasis. This study followed JBI recommendations for scoping reviews. Articles were searched on PubMed, Scopus, and Web of Science databases using keywords related to leishmaniasis and in silico methods for drug discovery, without publication date restrictions. The selection was based on primary studies involving computational methods for antileishmanial drug repurposing. Information about methodologies, obtained data, and outcomes were extracted. After the full-text appraisal, 34 studies were included in this review. Molecular docking was the preferred method for evaluating repurposing candidates (n=25). Studies reported 154 unique ligands and 72 different targets, sterol 14-alpha demethylase and trypanothione reductase being the most frequently reported. In silico screening was able to correctly pinpoint some known active pharmaceutical classes and propose previously untested drugs. Fifteen drugs investigated in silico exhibited low micromolar inhibition (IC50 < 10 µM) of Leishmania spp. in vitro. In conclusion, several in silico repurposing candidates are yet to be investigated in vitro and in vivo. Future research could expand the number of targets screened and employ advanced methods to optimize drug selection, offering new starting points for treatment development.

Keywords

• neglected tropical diseases
• computer-aided drug design
• repositioning
• docking
• molecular dynamics