Submission Details
Molecule(s):
C[C@]1(c2cccc(CNc3ccc4nnc(-c5ccccc5F)n4n3)c2)NC(=O)NC1=O
Cc1cc(-c2cc(C(=O)NCc3cccc([C@@]4(C)NC(=O)NC4=O)c3)c3c(C)noc3n2)c(C)o1
Nc1ncc2c(n1)CCN(C(=O)c1cc(F)cc3c(=O)c4cc(F)ccc4[nH]c13)C2
C[C@@]1(c2cccc(CNC(=O)[C@H]3CC(=O)N(c4cccc5ccccc45)C3)c2)NC(=O)NC1=O
O=C1NC(=O)/C(=N/c2cccc3c(O)nnc(O)c23)[C@@H](c2nc3ccccc3s2)C1=O
Cc1noc2nc(-c3ccc(F)cc3)cc(C(=O)NCc3cccc([C@@]4(C)NC(=O)NC4=O)c3)c12
O=C([C@@H]1C[C@@H]2CCCC[C@H]2N1C(=O)c1ccc(F)cc1F)N1CC=C(c2c[nH]c3ncccc23)CC1
C[C@@]1(c2cccc(C(=O)N3CCC[C@H](c4n[nH]c(-c5ccccc5)n4)C3)c2)NC(=O)NC1=O
C[C@@H](OC(=O)c1cc(-c2ccncc2)nc2ccccc12)C(=O)NC(=O)NC12CC3CC(CC(C3)C1)C2
Cc1ccc(-c2cc(C(=O)NCc3cccc([C@@]4(C)NC(=O)NC4=O)c3)c3c(C)noc3n2)cc1
Design Rationale:
Ten top virtual screening hits for Mpro as reported in Table S51. of an article "A multi-pronged approach targeting SARS-CoV-2 proteins using ultra-large virtual screening" by Gorgulla et al. (iScience 24, 102021, https://doi.org/10.1016/j.isci.2020.102021). Authors used "ultra-large-scale in silico screening platform, VirtualFlow, to search for inhibitors that target SARS-CoV-2". They screened roughly 1 billion molecules against targets including MPro. In Fig. S13 they show the predicted binding mode of their top compound which is very different compared to our leads: there is no direct interaction with His163. It might be interesting to check it out.
Other Notes:
LINK: https://www.cell.com/iscience/pdf/S2589-0042(20)31218-9.pdf