An early incarnation of the GA+Filter+SA approach was used to identify potential binders to the COVID-19 main protease (M Pro ) and submitted to the early stages of the COVID Moonshot project, a crowd-sourced initiative to accelerate the development of a COVID antiviral. Of the 10 submitted molecules, one was selected by the COVID Moonshot 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.