# Identification of Drug Repurposing Candidates for Coxsackievirus B3 Infection in iPSC-Derived Brain-like Endothelial Cells

## TL;DR

This study identifies potential drug candidates for treating Coxsackievirus B3 infection by analyzing how the virus affects brain endothelial cells.

## Contribution

A novel systems-level approach combining transcriptomic analysis and drug repurposing to identify MEK, PDGFR, and VEGF inhibitors as potential antiviral therapeutics.

## Key findings

- Coxsackievirus B3 infection alters host mRNA expression in brain endothelial cells, with downregulated ribosomal biogenesis and upregulated antiviral pathways.
- MEK, PDGFR, and VEGF inhibitors like pelitinib and neratinib are proposed as potential antiviral drugs targeting the blood–brain barrier.
- The study provides insights into Coxsackievirus B3-associated pathways and suggests new therapeutic strategies for this infection.

## Abstract

The enterovirus Coxsackievirus B3 causes a range of serious health problems, including aseptic meningitis, myocarditis, and pancreatitis. Currently, Coxsackievirus B3 has no targeted antiviral treatments or vaccines, leaving supportive care as the primary management option. Understanding how Coxsackievirus B3 interacts with and alters the blood–brain barrier may help identify new therapies to combat this often-devastating infection. We reanalyzed a previously published RNA sequencing dataset for Coxsackievirus B3-infected human-induced pluripotent stem-cell-derived brain endothelial cells (iBECs) to examine how Coxsackievirus B3 altered mRNA expression. By integrating GSEA, EnrichR, and iLINCs-based perturbagen analysis, we present a novel, systems-level approach to uncover potential drug repurposing candidates for CVB3 infection. We found dynamic changes in host transcriptomic response to Coxsackievirus B3 infection at 2- and 5-day infection time points. Downregulated pathways included ribosomal biogenesis and protein synthesis, while upregulated pathways included a defense response to viruses, and interferon production. Using iLINCs transcriptomic analysis, MEK, PDGFR, and VEGF inhibitors were identified as possible novel antiviral therapeutics. Our findings further elucidate Coxsackievirus B3-associated pathways in (iBECs) and highlight potential drug repurposing candidates, including pelitinib and neratinib, which may disrupt Coxsackievirus B3 pathology at the blood–brain barrier (BBB).