For Round 3 we use Glide SP rather than HTVS for the GA search, use Molecule.one in addition to ASKCOS to determine synthetic accessibility for molecules with XP scores better than -7.0, and eliminate all molecules with for which both ASKCOS and Molecule.one fail to find a retrosynthetic route. The remaining 136 molecules are then re-docked using the XP scoring methodology and molecules are selected from among the top-scoring molecules. We selected four molecules for submission to Round 3 (Figure ) based on their score, diversity (also relative to our Round 2 submissions), and size and submitted them to Round 3 on April 2nd, 2020. (We also submitted four molecules selected based purely on their score, i.e. with synthetic accessibility considerations based on ASKCOS and Molecule.one, which are not discussed further.) Of the 10 submitted molecules, one was selected by the organizers (Figure ) for synthesis and assay, but showed relatively low inhibition (10% average inhibition at 20 µM) and was not pursued further. Many of our submissions feature a urea linkage or amide linkage that are also present in many of the fragment binders identified by the COVID Moonshot organizers (Figure ). In fact one of our submissions (Figure ) differs by only a few atoms from one of the fragments (Figure ) as well as one the submissions selected for further study. Overall, these results are quite encouraging given that our submissions are generated starting from randomly selected molecules.