# A reanalysis and integration of transcriptomics and proteomics datasets unveil novel drug targets for Mekong schistosomiasis

## TL;DR

This study identifies focal adhesion kinase (FAK) as a potential new drug target for treating Mekong schistosomiasis, a parasitic disease.

## Contribution

The study proposes FAK as a novel drug target for schistosomiasis and identifies specific FAK inhibitors with anti-parasitic activity.

## Key findings

- FAK is upregulated in S. mekongi and plays a key role in cellular processes, making it a promising drug target.
- FAK inhibitors 14 and PF-03814735 showed strong binding to Schistosoma FAK with minimal binding to human FAK.
- In vitro assays demonstrated significant anti-parasitic activity against multiple Schistosoma species with low human cell toxicity.

## Abstract

Schistosomiasis, caused by Schistosoma trematodes, is a significant global health concern, particularly affecting millions in Africa and Southeast Asia. Despite efforts to combat it, the rise of praziquantel (PZQ) resistance underscores the need for new treatment options. Protein kinases (PKs) are vital in cellular signaling and offer potential as drug targets. This study focused on focal adhesion kinase (FAK) as a candidate for anti-schistosomal therapy. Transcriptomic and proteomic analyses of adult S. mekongi worms identified FAK as a promising target due to its upregulation and essential role in cellular processes. Molecular docking simulations assessed the binding energy of FAK inhibitors to Schistosoma FAK versus human FAK. FAK inhibitor 14 and PF-03814735 exhibited strong binding to Schistosoma FAK with minimal binding for human FAK. In vitro assays confirmed significant anti-parasitic activity against S. mekongi, S. mansoni, and S. japonicum, comparable to PZQ, with low toxicity in human cells, indicating potential safety. These findings highlight FAK as a promising target for novel anti-schistosomal therapies. However, further research, including in vivo studies, is necessary to validate efficacy and safety before clinical use. This study offers a hopeful strategy to combat schistosomiasis and reduce its global impact.