Topic automatically created for discussing the designs at:
https://covid.postera.ai/covid/submissions/PET-UNK-3324058f
As promised in the submission notes here is some discussion of the structure of the MPro complex with MAT-POS-4223bc15-23 and this comment on EDJ-MED-015fb6b4-2 may also be relevant. A number of replacements for the pendant amide on a dihydropyridone scaffold are presented in the PET-UNK-37251634 | PET-UNK-d62a9a75 | PET-UNK-4d432d33 submissions and each of these has an unsaturated carbon corresponding to the carbonyl carbon of the pendant amide. I would not expect any of these replacements for the pendant amide to work well on the tetrahydroisoquinoline scaffold since none has a hydrogen bond donor that stabilizes the bound conformation.