The Moonshot project has accumulated several synthetically accessible virtual libraries that would be very interesting to computationally screen for whether they might contain good “magic merges” of fragments from the X-ray fragment screen against Mpro.
It would be fantastic if the folks who have developed methods to look for fragment merges (@dmoustakas @matteoferla @tdudgeon and others) would be able to screen these datasets and report the top interesting hits:
Fragment Network expansions: @tdudgeon has enumerated compounds from Molport and Chemspace that contain the fragment hits as a substructure using the Fragment Network approach (code here). The largest set contains 85K compounds.
expanded-22_hac0-10_rac0-3_hops3.smi (2.6 MB)
London Ugi acrylamide library: @londonir has enumerated a library of Ugi reaction products accessible via parallel synthesis that possess an acrylamide warhead. There are ~39K compounds in this library.
ugi-enumeration.smi (3.2 MB)
London noncovalent pyridine-urea library: @londonir has enumerated a library of 15,279 non-covalent pyridine-ureas based on the fragment from x0434 that Enamine could make in parallel.
pyridine_urea.smi (623.4 KB)
London covalent piperadine-amide chloracetamide library: @londonir has enumerated a library of ~35K compounds for a covalent series for which there are three fragment structures (x1358, x1380, x1458).
piperidine-amides.smi (1.8 MB)
If any of these libraries contain high-quality fragment merges, it may be possible to rapidly synthesize some of them to test the fragment merge hypothesis.