# A High-Throughput Antiviral Assay Based on a Sindbis Virus-GFP for the Discovery of Inhibitors of Alphavirus Replication

## TL;DR

This paper introduces a high-throughput assay using a modified Sindbis virus to screen for antivirals against alphaviruses like chikungunya.

## Contribution

A novel high-throughput antiviral screening assay using a Sindbis virus-GFP model for safer and efficient alphavirus drug discovery.

## Key findings

- The Sindbis virus-GFP assay is reproducible and validated with known antiviral compounds.
- High-content imaging enables efficient antiviral screening at lower biosafety levels.
- The assay serves as a safer alternative for studying more pathogenic alphaviruses.

## Abstract

The re-emergence of alphaviruses (family Togaviridae), such as chikungunya virus, poses significant public health risks, with direct impact on quality of life and work productivity. There are no approved antiviral drugs for the treatment of infections with alphaviruses. Several alphaviruses are classified as risk group 3 agents which require handling in high-containment laboratories. To facilitate antiviral screening efforts against alphaviruses, we established a high-throughput antiviral screening assay using reporter Sindbis virus [SINV-GFP; expresses the green fluorescent protein] as a surrogate model for more pathogenic alphaviruses. The assay has strong reproducibility and was validated by reference small-molecule antivirals with various mechanisms of action. The use of high-content imaging as a readout, as demonstrated here, allows for high-throughput antiviral screening and provides a tool for early-stage antiviral discovery against emerging alphavirus threats at a lower biosafety level.