To assess the overall quality of combinations from Fragmenstein, i.e. determining the methodological failure rate and synthetic accessibility, two targets, MPro (a cysteine protease from SARS-COV-2) and Mac1 (a nucleosyl-peptide hydrolase from SARS-COV-2) from previous fragment screens were chosen and the initial hits that originated from a library designed to facilitate synthetic derivatives (DSi-Poised) were combined and scored (Table , interactive at DSiP). Excluding the combinations that were over 5Å apart for their closest atoms, the failure rate was 1.4% due to compounds whose chemistry could not be rectified correctly, while 56% of combinations were energetically favourable (∆∆G < 0) without excessive deviation from the positions of the parent hits (RMSD < 1.). Of the 420 acceptable combinations, 7 were purchasable, while 64 could potentially be made with 2 or fewer reactions according to predictions from PostEra Manifold . Therefore, Fragmenstein suggests synthetically accessible compounds that are predicted to follow the binding conformation of the parent fragment hits, which is an underpinning assumption in fragment-based drug discovery (cf. Figure ).