High content screening strategies for large-scale compound libraries with a focus on high-containment viruses

A majority of viral diseases do not have FDA-approved drugs. The recent outbreaks caused by SARS-CoV-2, monkeypox, and Sudan ebolavirus have exposed the critical need for rapid screening and identification of antiviral compounds against emerging/re-emerging viral pathogens. A high-content screening (HCS) platform is becoming an essential part of the drug discovery process, thanks to developments in image acquisition and analysis. While HCS has several advantages, its full potential has not been realized in antiviral drug discovery compared to conventional drug screening approaches, such as fluorescence or luminescence-based microplate assays. Therefore, this review aims to summarize HCS workflow, strategies, and developments in image-based drug screening, focusing on high-containment viruses.