For Round 2 we perform 20 GA searches with a population size of 400 using the HTVS+Filter+SA as above and the 6LU7 crystal structure of M Pro . However, at that early stage we sampled our initial population from the first 1000 molecules of the 250K ZINC database subset. Also, we were not yet aware of the importance of neutralizing acid base groups before computing the SA score and checking synthetic accessibility, but this does not seem to be important for this target. Based on experience with the other targets we did increase the maximum molecule size to 50 ± 5 non-hydrogen atoms. All molecules in the final population are re-scored using the Glide XP scoring function . The 128 molecules with a score better than or equal to -7.0 are selected and subjected to retrosynthetic analysis using the ASKCOS software package using the settings suggested by Gao and Coley . Molecules with less than 4 synthetic steps are selected and re-docked using the XP scoring methodology. The six molecules with XP scores better than -7.5 (Figure )a-f were then submitted to Round 2 in March 30th, 2020. The feedback on Twitter was that the molecules were rather small and more fragment-like than drug-like.