Hit rate. With the four-stage procedure described above (see Section 2.1), 27 compounds were found to be inhibitors (see Figure and Table ) across all SARS-CoV-2 protein targets. The experimental testing is described in the following paragraphs. Due to the multiple team submissions and the compound selection procedure some teams submitted compounds which were tested on a target which is different to the suggested one. We tackle this issue by providing a) an analysis for which these compounds are excluded (Table and Table ) and b) an analysis for which these compounds are included (Supporting Information Section 3). For a) 14 hits had been suggested by the team jku and bind to Nsp5 (see Table ). This amounts to a hit rate of 20.9% [95% confidence interval: 11.9-32.6%] (14 actives of 67 tested) of the best team, which is followed by the teams kyuken with a hit rate of 7.1% [2.0-17.3%] (4 actives out of 56 tested) and aiwinter with a hit rate of 5.0% [0.1-24.9%] (1 active out of 20 tested). Note that three different types of assays, a) in vitro (cell-free or live cell) activity, b) biophysical binding and c) x-ray crystallography, have been used to experimentally test the compounds (see Section 2.6). Novelty of hits. To evaluate the novelty of the found hits, the hit compounds are compared to prior-art molecules, which are molecules either used in filtering operations such as similarity searches or used as an active training instance for Machine Learning methods by any of the teams. The activity cut-offs for the metrics pKi, pKd, pIC50 and pChEMBL were set to 6.3. Scatterplots in t-SNE coordinates (Figure and Figure ) show the relative location of the hit compounds in comparison to the prior-art compounds. Notably, compared to Nsp12 and S, Nsp3 and Nsp5 contain many prior-art molecules, due to the availability of SARS-CoV data that was assumed by the teams to be similar (in terms of binding sites) as compared to SARS-CoV-2. The hits identified by jku (14 compounds) and aiwinter (1 compound) build a cluster and overlap in the Nsp5 scatterplot. Looking in more detail we find many benzotriazolyl acetamide derivatives in the prior art data in this cluster (Figure ). The benzotriazole family had been considered indeed for SARS-CoV in 2008 by Verschueren , with published protein databank structures. For secondary clusters of hits (e.g., cermn & virtualflow; lower left quadrant of Nsp5 scatter plot in Figure ), we could not identify similar functional groups or motifs in the proximal prior art compounds. The S hits (kyuken and deeplab) and Nsp12 hit compound (imolecule) do not reside in the neighborhood of prior art compounds which is why they can be considered as highly novel (Figure ). For targets other than Nsp5, too few hits were found to draw statistically relevant conclusions on cluster size or novelty.