Submission Details
Molecule(s):
O=C1NCCC1=CC(=O)N1Cc2ccccc2[C@H](c2cccc(Cl)c2)C1
O=C1NCCC1=CC(=O)N1Cc2ccccc2[C@H](c2ccccc2)C1
CN(C)C(=O)C=CC(=O)N1Cc2ccccc2[C@H](c2cccc(Cl)c2)C1
N#CC(=CC(=O)N1Cc2ccccc2[C@H](c2ccccc2)C1)c1cscn1
N#CC(=CC(=O)N1Cc2ccccc2[C@H](c2ccccc2)C1)c1cc[nH]n1
Design Rationale:
Mpro-x1392 was chosen as start structure with the aim to change the electrophile away from chloroacetamide and to fill the S1 pocket. The proposed designs all fill this area of the site better than the start fragment, which leaves it untargeted. The nitrile-containing electrophile moieties are designed reminiscent of the covalently reversible warheads of Taunton and coworkers. See one examplary binding pose attached (PDB).
Other Notes:
Joint submission Rainer Wilcken & Callum Dickson