Dr. Fernando J. Montero Segovia and his team at the University of Granada, Spain, are researching ways to mitigate COVID-19 virulence by targeting the interaction between the PALS1 protein and the SARS-CoV-2 Envelope (E) protein. This interaction is crucial for the virus’s ability to disrupt tight junctions, a key factor in COVID-19 pathogenesis.
Supported by EU-OPENSCREEN, the team utilized screening services at the University of Helsinki’s Institute of Molecular Medicine Finland (FIMM). They conducted a large-scale screening of the EU-OPENSCREEN compound library using an AlphaScreen assay to identify inhibitors that disrupt the PALS1-PDZ interaction.
From an initial pool of 100,000 compounds, the screening identified 345 positive hits. These findings represent a significant advancement in developing small-molecule inhibitors targeting the PALS1-PDZ interaction. The lead compounds discovered hold promise for creating broad-spectrum antiviral agents with reduced susceptibility to resistance development.
By inhibiting the PALS1/SARS-CoV-2-E interaction, these compounds can potentially reduce the virulence of SARS-CoV-2 and other coronaviruses, providing valuable tools for subsequent scientific investigations. These studies will evaluate the toxicity and impact of PALS1 inhibition on normal cellular function, contributing to understanding the cellular roles of PALS1 in coronavirus pathogenesis.
ISIDORe’s support has been crucial in achieving these results, highlighting the importance of collaborative efforts in advancing pandemic preparedness and response. This research not only addresses current challenges posed by SARS-CoV-2 but also prepares for future zoonotic outbreaks by developing novel antiviral strategies targeting host proteins.