Catalogue Compounds - StructuralGenomicsConsortium/CNP25-CHIKV-nsP3-Macrodomain GitHub Wiki

The 'catalogue compounds' are derived from manual and algorithmic fragment merges that were directly available (or as close analogues) to buy from Enamine. We reviewed the generated fragment merges regarding their potential interactions with the nsP3 macrodomain and their similarity to the original fragments before ordering 85 compounds.

These compounds were ordered as crudes and pures (only 79 out of 85 were made) from Enamine for binding analysis by high-throughput crystallography and GCI.

Crystallography

Binding could be detected for 10 of the 85 'catalogue compounds'.

GCI

The 79 purified catalogue compounds were tested by GCI in the format of single concentration screen and dose titration. When screened at 100µM (in duplicates), 27 compounds were found to show signs of binding by having comparatively higher level of surface mass (Response pg/mm2)

Screen of Compound 1-40

Screen of Compound 41-79

6 (circled in green) of the 27 detected compounds were also observed in the Nsp3 crystal structure, however, only 7 (circled in yellow) out of 14 compounds (previously detected as hits by GCI screened at 25µM) showed up as hits again in the 100µM screen.

Dose titration experiments on the hit compounds that were also found in crystal structures took priority