As in CACHE #1, the participating teams used a diverse array of workflows. Overall, hit rates were low compared with virtual screening results typically reported in the literature, with no clear benefit of using methods supplemented by machine-learning over purely physics-based methods. Nevertheless, 13 experimentally validated Nsp13-targeting chemical series (binding affinities ranging from 1 to 90 µM) were identified by 11 different teams, representing starting points for the development of chemical probes to explore the antiviral effect of Nsp13 inhibition.