Identification of viroporin blockers for future antiviral therapy using automated high-throughput screening

The potential for future viral pandemics to trigger a global crisis underscores the urgent need for the development of new antiviral drugs. Viroporins, identified in several RNA virus families, form pores/ion channels in cell and/or virus membranes, contributing to the virus life cycle and virus-induced pathology. Blocking viroporins with small-molecule compounds has proven to be an effective therapeutic strategy. However, the clinical success of these viroporin blockers has been limited due to emerging resistance and insufficient potency when repurposed for other viroporin targets. Expanding the repository of viroporin blockers by identifying new compounds that potently inhibit virus infections will advance the pandemic preparedness and likely make drug repurposing more successful in the future. A major challenge is the current methodology for exploring viroporin blockers, which is traditionally time-consuming and has low throughput. In this project. we will combine our novel viroporin inhibitor assay with an automated high-throughput screening (HTS) platform and a library of 50,000 compounds, creating a pipeline suitable for identifying new blockers of potentially any given viroporin. Our pipeline consists of four steps: (I) the identification of viroporin targets, (II) HTS, (III) cross-validation and (IV) and hit-to-lead optimization. Preliminary data from our group demonstrates the feasibility of the assay for viroporins from viruses relevant to global health. We plan to screen relevant viroporins in HTS to develop novel, high potency viroporin inhibitors and file intellectual property (IP) for rationally optimized hit compounds. Once the IP is filed, we will establish a spin-out company to raise funds from public and private sources, advancing our proof-of-concept studies and developing the lead compound further.