April 25th 2024

Published in Antiviral Res: A new image-based and high-throughput platform to identify broad-spectrum coronavirus antivirals

Published in Antiviral Res: A new image-based and high-throughput platform to identify broad-spectrum coronavirus antivirals

The CARE member, Johnson & Johnson Innovative Medicine, developed a high-content imaging platform compatible with high-throughput screening, with the aim of identifying compounds with antiviral activity and to deprioritize those that induce undesirable phenotypes in host cells.

The immunofluorescence-based assay to assess the antiviral compounds against coronaviruses was adapted for high-throughput screening by shortening assay run times, miniaturizing well size and volumes, combining permeabilization and staining steps, and by using automated image analysis. The inclusion of cellular dyes and immunostaining in combination with in-depth image analysis enabled identification of compounds that induced undesirable phenotypes in host cells, such as changes in cell morphology or in lysosomal activity.

This platform was easily adapted to different SARS-CoV-2 variants (B1, Omicron BA.5 and Omicron XBB.1.5), SARS-CoV and human coronavirus 229E using different antibodies and cell types. With the platform, ~900K compounds were screened and hits were triaged in just four weeks, thereby allowing the identification of potential anti-coronaviral compounds carrying broad-spectrum activity with limited off-target effects.

This new platform is broadly applicable as it can be adapted to include various cell types, viruses, antibodies, and dyes. By developing and running the antiviral assay against different coronavirus strains, it was demonstrated that the assay can most likely be efficiently adapted to test against new SARS-CoV-2 variants or new coronavirus species as soon as they emerge. Given the high risk for future coronavirus outbreaks or other pandemics from new zoonotic reservoirs, the flexibility and broad applicability of this assay are of particular interest.

To learn more, click here: A flexible, image-based, high-throughput platform encompassing in-depth cell profiling to identify broad-spectrum coronavirus antivirals with limited off-target effects