The biophysical data and structure-activity relationship (SAR) of Round 1 hits and their Round 2 analogs were evaluated by an independent Hit Evaluation Committee composed of industry experts in biophysics, medicinal chemistry and computational chemistry (Table ), leading to a final score assigned to each Round 1 hit (Table ). Overall, 13 compounds had a score greater than 10 (Table ), reflecting robust experimental confirmation, which corresponds to a hit rate of 0.7%. The computational workflows of CACHE #2 participants were then evaluated based on the aggregated score of Round 1 compounds, and based on the best scoring Round 1 molecule (Figure ,b, Table ). In a separate evaluation scheme, all participants were asked to predict Nsp13 ligands from the merged collection of 1957 Round 1 compounds before the experimental data were generated. The aggregated score of predicted hits, normalized based on the number of hits predicted, was used to rate the computational workflows (Figure ). This scheme is complementary as here, all teams predicted hits from the same library, while in Rounds 1 and 2, participants screened compound collections from the Enamine catalog that may vary widely in size to best align with their computational methods and resources. ).