Description

COVID Moonshot Sprint 10 for P1 pocket replacement based on x10959 (ADA-UCB-6c2cb422-1) to optimize substituents in the P1 pocket with Mpro dimer and neutral Cys145:His41 catalytic dyad

Progress

100.00%

Distributions

relative free energy distribution cumulative free energy distribution

Leaderboard

Rank Compound SMILES ΔG / kcal mol-1 pIC50
1 DAR-DIA-56cf811e-1 molecule C#CC(=O)N(c1cncc2c1cccc2)C(=O)Cc3cccc(c3)Cl −13.7 ± 0.2 10.0 ± 0.1
2 TRY-UNI-9f475305-8 molecule Cc1cc(no1)CN(C(=O)C(C)c2cccc(c2)Cl)C(=O)NC3CC3 −13.7 ± 0.2 10.0 ± 0.2
3 PET-UNK-12d8d43f-2 molecule COC(=O)N(c1cncc2c1cccc2)C(=O)Cc3cccc(c3)Cl −12.8 ± 0.2 9.4 ± 0.1
4 JOH-UNI-a38a7bdd-7 molecule Cc1ccncc1N(C(=O)Cc2cccc(c2)Cl)C(=O)C3CC3C(F)(F)F −11.2 ± 0.2 8.1 ± 0.1
5 JIN-POS-6dc588a4-16 molecule c1cc(cc(c1)Cl)CC(=O)Nc2c3ccncc3on2 −10.85 ± 0.10 7.91 ± 0.07
6 PET-UNK-a692de38-1 molecule c1ccc2c(c1)cncc2N(C(=O)Cc3cccc(c3)Cl)NC#N −10.5 ± 0.2 7.6 ± 0.2
7 EDJ-MED-c8e7a002-13 molecule c1cc(cc(c1)Cl)CC(=O)Nc2c3c(cccc3F)n[nH]2 −10.1 ± 0.1 7.4 ± 0.1
8 PET-UNK-1320d94d-29 molecule CN([C@H](c1cccc(c1)Cl)C(=O)Nc2cncc3c2cccc3)C(=O)[C@@H]4CCC[C@@H](O4)C(=O)N5CCCC5 −10.1 ± 0.3 7.3 ± 0.2
9 EDJ-MED-c8e7a002-17 molecule c1cc(cc(c1)Cl)CC(=O)Nc2c3nnc(n3cnc2Cl)O −10.05 ± 0.10 7.32 ± 0.07
10 EDJ-MED-c8e7a002-7 molecule c1cc(cc(c1)Cl)CC(=O)Nc2c3nncn3cnc2Cl −9.8 ± 0.1 7.1 ± 0.1
11 ALP-POS-3b848b35-4 molecule c1ccc2c(c1)cncc2NC(=O)C(CCC3CCCCC3)c4cccc(c4)Cl −9.5 ± 0.2 6.9 ± 0.2
12 DAR-DIA-076fb6ea-5 molecule c1ccc2c(c1)cncc2N(C#CC#N)C(=O)Cc3cccc(c3)Cl −9.5 ± 0.5 6.9 ± 0.3
13 PET-UNK-12d8d43f-1 molecule c1ccc2c(c1)cncc2N(C=O)C(=O)Cc3cccc(c3)Cl −9.5 ± 0.1 6.89 ± 0.09
14 SAM-UNK-2684b532-3 molecule Cc1ccncc1NC(=O)C(c2cccc(c2)Cl)c3nnc(s3)C −9.4 ± 0.1 6.86 ± 0.10
15 PET-UNK-ac320b15-7 molecule c1ccc2c(c1)cncc2NC(=O)[C@@H](c3cccc(c3)Cl)NC(=O)[C@@H]4CC[C@H](O4)C(=O)N5CCCC5 −9.3 ± 0.2 6.8 ± 0.1
16 MIC-UNK-d36ab305-4 molecule CN(C)c1ccc(cc1)C(c2cccc(c2)Cl)C(=O)Nc3cncc4c3cccc4 −9.2 ± 0.2 6.7 ± 0.1
17 PET-UNK-5ecb6237-1 molecule c1ccc2c(c1)cncc2N(C#N)C(=O)Cc3cccc(c3)Cl −9.2 ± 0.1 6.7 ± 0.1
18 MIC-UNK-c66144cb-1 molecule c1ccc2c(c1)cncc2NC(=O)C(CCc3cccc(c3)F)c4cccc(c4)Cl −9.1 ± 0.2 6.6 ± 0.2
19 MIC-UNK-c66144cb-3 molecule c1ccc2c(c1)cncc2NC(=O)C(CCC3CCCCC3)c4cccc(c4)Cl −9.1 ± 0.2 6.6 ± 0.2
20 DAR-DIA-076fb6ea-15 molecule c1ccc2c(c1)cncc2N(C(=O)Cc3cccc(c3)Cl)N=C=S −9.1 ± 0.2 6.6 ± 0.1
21 JAN-GHE-5a013bed-9 molecule c1cc(cc(c1)Cl)CC(=O)Nc2cncnc2 −9.1 ± 0.1 6.61 ± 0.09
22 RUB-POS-1325a9ea-18 molecule c1ccc2c(c1)cnc(c2NC(=O)Cc3cccc(c3)Cl)F −9.06 ± 0.04 6.60 ± 0.03
23 PET-UNK-1320d94d-7 molecule c1ccc2c(c1)cncc2NC(=O)[C@@H](c3cccc(c3)Cl)NC(=O)[C@@H]4C[C@@H](O4)C(=O)N5CCCC5 −9.0 ± 0.2 6.6 ± 0.2
24 PET-UNK-1320d94d-5 molecule c1ccc2c(c1)cncc2NC(=O)[C@@H](c3cccc(c3)Cl)NC(=O)[C@@H]4CC[C@@H](O4)C(=O)N5CCC5 −9.0 ± 0.2 6.6 ± 0.1
25 PET-UNK-ac320b15-5 molecule c1ccc2c(c1)cncc2NC(=O)[C@@H](c3cccc(c3)Cl)NC(=O)[C@H]4CC[C@@H](O4)C(=O)N5CCCC5 −9.0 ± 0.2 6.5 ± 0.1
26 PET-UNK-1320d94d-9 molecule c1ccc2c(c1)cncc2NC(=O)[C@@H](c3cccc(c3)Cl)NC(=O)[C@@H]4CCC[C@@H](O4)C(=O)N5CCCC5 −9.0 ± 0.2 6.5 ± 0.2
27 VLA-UNK-dc1d9354-1 molecule c1ccc2c(c1)[nH]c(=O)n2NC(=O)Cc3cccc(c3)Cl −9.0 ± 0.2 6.5 ± 0.1
28 JAN-GHE-5a013bed-4 molecule c1cc(cc(c1)Cl)CC(=O)Nn2cn[nH]c2=O −8.9 ± 0.1 6.51 ± 0.10
29 JAN-GHE-f4ca5a00-18 molecule CCCCC(c1cccc(c1)Cl)C(=O)Nn2cncc2C3CC3 −8.8 ± 0.2 6.4 ± 0.1
30 PET-UNK-6314f867-3 molecule c1cc(cc(c1)Cl)CC(=O)Nc2cncc3c2c(ccc3)C#N −8.8 ± 0.1 6.43 ± 0.09
31 EDJ-MED-076d6e64-1 molecule c1cc(cc(c1)Cl)CC(=O)Nc2cncn3c2nnc3 −8.8 ± 0.1 6.42 ± 0.09
32 PET-UNK-1320d94d-21 molecule CN(C)C(=O)[C@H]1CC[C@H](O1)C(=O)N(C)[C@H](c2cccc(c2)Cl)C(=O)Nc3cncc4c3cccc4 −8.8 ± 0.2 6.4 ± 0.2
33 TRY-UNI-9f475305-3 molecule Cc1ccncc1NC(=O)C(c2cccc(c2)Cl)c3nnc(s3)C −8.8 ± 0.1 6.41 ± 0.09
34 JAN-GHE-f4ca5a00-20 molecule CCCCC(c1cccc(c1)Cl)C(=O)Nn2c(cnn2)C3CC3 −8.8 ± 0.2 6.4 ± 0.1
35 ADA-UCB-6c2cb422-11 molecule COc1ccccc1CO[C@@H](c2cccc(c2)Cl)C(=O)Nc3cc(=O)[nH]c4c3cccc4 −8.8 ± 0.2 6.4 ± 0.2
36 MAT-POS-7174c657-6 molecule c1ccc2c(c1)cncc2NC(=O)[C@@H](c3cccc(c3)Cl)NC(=O)[C@@H]4CC[C@@H](O4)C(=O)N5CCCC5 −8.8 ± 0.2 6.4 ± 0.2
37 DAR-DIA-56cf811e-4 molecule Cc1ccncc1N(C(=O)Cc2cccc(c2)Cl)C(=O)/C=C/C#N −8.7 ± 0.2 6.4 ± 0.1
38 JAN-GHE-83b26c96-7 molecule Cc1c(cncn1)NC(=O)C(c2cccc(c2)Cl)C(C)C −8.7 ± 0.2 6.3 ± 0.1
39 PET-UNK-1320d94d-24 molecule CN([C@@H](c1cccc(c1)Cl)C(=O)Nc2cncc3c2cccc3)C(=O)[C@@H]4CC[C@@H](O4)C(=O)N5CCOCC5 −8.7 ± 0.2 6.3 ± 0.2
40 EDJ-MED-ee07cf00-11 molecule c1ccc2c(c1)cncc2NC(=O)C(c3cccc(c3)Cl)NC(=O)C4CCC(O4)C(=O)N5CCCC5 −8.7 ± 0.1 6.32 ± 0.09
41 EDJ-MED-c8e7a002-8 molecule c1cc(cc(c1)Cl)CC(=O)Nc2c3nnnn3cnc2Cl −8.6 ± 0.1 6.3 ± 0.1
42 MIC-UNK-5a93dd5f-12 molecule c1ccc2c(c1)cncc2NC(=O)C(c3cccc(c3)Cl)N4CCC(C4)N5CCCCC5 −8.63 ± 0.09 6.29 ± 0.07
43 ALP-POS-95b75b4d-6 molecule c1cc(cc(c1)Cl)CC(=O)Nc2cnccc2O −8.6 ± 0.1 6.27 ± 0.09
44 MIC-UNK-c66144cb-2 molecule c1ccc2c(c1)cncc2NC(=O)C(CCc3ccc(cc3)F)c4cccc(c4)Cl −8.6 ± 0.2 6.3 ± 0.1
45 JAN-GHE-5a013bed-2 molecule c1ccc2c(c1)ncn2NC(=O)Cc3cccc(c3)Cl −8.56 ± 0.07 6.24 ± 0.05
46 PET-UNK-1320d94d-26 molecule CN([C@@H](c1cccc(c1)Cl)C(=O)Nc2cncc3c2cccc3)C(=O)[C@@H]4CC[C@@H](O4)C(=O)N5CCC5 −8.6 ± 0.2 6.2 ± 0.2
47 VLA-UNK-9a7dc93f-7 molecule COC(c1cccc(c1)Cl)C(=O)Nc2cncc3c2cccc3 −8.53 ± 0.05 6.21 ± 0.03
48 EDJ-MED-97c1bf5c-2 molecule COc1c(c2nnnn2cn1)NC(=O)Cc3cccc(c3)Cl −8.4 ± 0.1 6.13 ± 0.08
49 PET-UNK-1320d94d-25 molecule CN([C@H](c1cccc(c1)Cl)C(=O)Nc2cncc3c2cccc3)C(=O)[C@@H]4CC[C@@H](O4)C(=O)N5CCC5 −8.4 ± 0.2 6.1 ± 0.2
50 MAT-POS-a13804f0-4 molecule c1ccc2c(c1)cncc2NC(=O)C(c3cccc(c3)Cl)NC(=O)[C@@H]4CC[C@@H](O4)C(=O)N5CCCC5 −8.38 ± 0.09 6.11 ± 0.06
51 JAN-GHE-f4ca5a00-17 molecule c1cc(cc(c1)Cl)CC(=O)Nn2c(cnn2)C3CC3 −8.4 ± 0.1 6.10 ± 0.10
52 VLA-UNK-411a133b-1 molecule Cn1nc(nn1)NC(=O)Cc2cccc(c2)Cl −8.4 ± 0.1 6.10 ± 0.09
53 MAT-POS-bb423b95-8 molecule c1cc(cc(c1)Cl)CC(=O)Nc2cncc3c2ccc(c3)O −8.4 ± 0.1 6.08 ± 0.08
54 PET-UNK-1320d94d-6 molecule c1ccc2c(c1)cncc2NC(=O)[C@H](c3cccc(c3)Cl)NC(=O)[C@@H]4CC[C@@H](O4)C(=O)N5CCC5 −8.3 ± 0.2 6.1 ± 0.1
55 MAK-UNK-c749d764-6 molecule CC(CNCCCO)C(c1cccc(c1)Cl)C(=O)Nc2cncc3c2cccc3 −8.3 ± 0.2 6.1 ± 0.2
56 RUB-POS-1325a9ea-17 molecule c1ccc2c(c1)c(cnc2F)NC(=O)Cc3cccc(c3)Cl −8.34 ± 0.04 6.08 ± 0.03
57 PET-UNK-ac320b15-9 molecule c1ccc2c(c1)cncc2NC(=O)[C@@H](c3cccc(c3)Cl)NC(=O)[C@H]4CC[C@H](O4)C(=O)N5CCCC5 −8.3 ± 0.2 6.1 ± 0.1
58 EDJ-MED-ee07cf00-7 molecule Cc1c(c(=O)ccn1CC(=O)NC(c2cccc(c2)Cl)C(=O)Nc3cncc4c3cccc4)O −8.3 ± 0.2 6.0 ± 0.2
59 PET-UNK-1320d94d-1 molecule CN(C)C(=O)[C@H]1CC[C@H](O1)C(=O)N[C@H](c2cccc(c2)Cl)C(=O)Nc3cncc4c3cccc4 −8.3 ± 0.2 6.0 ± 0.1
60 PET-UNK-1320d94d-3 molecule c1ccc2c(c1)cncc2NC(=O)[C@@H](c3cccc(c3)Cl)NC(=O)[C@@H]4CC[C@@H](O4)C(=O)N5CCOCC5 −8.2 ± 0.2 6.0 ± 0.1
61 MIC-UNK-50cce87d-3 molecule Cc1cccc2c1c(cnc2)NC(=O)Cc3cccc(c3)Cl −8.18 ± 0.07 5.96 ± 0.05
62 MIC-UNK-d36ab305-1 molecule CC(=O)Nc1ccc(cc1)C(c2cccc(c2)Cl)C(=O)Nc3cncc4c3cccc4 −8.2 ± 0.2 6.0 ± 0.1
63 PET-UNK-1320d94d-2 molecule CN(C)C(=O)[C@H]1CC[C@H](O1)C(=O)N[C@@H](c2cccc(c2)Cl)C(=O)Nc3cncc4c3cccc4 −8.2 ± 0.2 5.9 ± 0.2
64 EDJ-MED-ee07cf00-2 molecule Cc1c(c(=O)n2c(n1)cc[nH]2)CC(=O)NC(c3cccc(c3)Cl)C(=O)Nc4cncc5c4cccc5 −8.1 ± 0.2 5.9 ± 0.1
65 PET-UNK-ac320b15-8 molecule c1ccc2c(c1)cncc2NC(=O)[C@H](c3cccc(c3)Cl)NC(=O)[C@@H]4CC[C@H](O4)C(=O)N5CCCC5 −8.1 ± 0.2 5.9 ± 0.2
66 PET-UNK-6314f867-2 molecule c1cc(cc(c1)Cl)CC(=O)Nc2cncc3c2ccc(c3)C#N −8.1 ± 0.1 5.90 ± 0.10
67 ALP-POS-a9ad2217-2 molecule CN(C(c1cccc(c1)Cl)C(=O)Nc2cncc3c2cccc3)C(=O)[C@@H]4CC[C@@H](O4)C(=O)N5CCCC5 −8.1 ± 0.2 5.9 ± 0.2
68 PET-UNK-1320d94d-27 molecule CN([C@H](c1cccc(c1)Cl)C(=O)Nc2cncc3c2cccc3)C(=O)[C@@H]4C[C@@H](O4)C(=O)N5CCCC5 −8.0 ± 0.2 5.9 ± 0.2
69 MIC-UNK-5a93dd5f-1 molecule c1ccc2c(c1)cncc2NC(=O)C(c3cccc(c3)Cl)N4CC5CCCC5C4 −8.0 ± 0.2 5.9 ± 0.1
70 MAT-POS-bfb445d4-2 molecule c1ccc2c(c1)nnn2NC(=O)Cc3cccc(c3)Cl −8.00 ± 0.08 5.83 ± 0.06
71 JIN-POS-6dc588a4-17 molecule c1cc(cc(c1)Cl)CC(=O)Nc2cc3nccn3cn2 −8.0 ± 0.2 5.8 ± 0.1
72 JOH-UNI-ee5ed7c8-6 molecule c1ccc2c(c1)cncc2NC(=O)C(CC#N)c3cccc(c3)Cl −8.0 ± 0.1 5.81 ± 0.09
73 JIN-POS-6dc588a4-11 molecule c1cc(cc(c1)Cl)CC(=O)Nc2cncc3c2ccc(c3)F −7.98 ± 0.07 5.81 ± 0.05
74 ALP-POS-3fc1724e-8 molecule c1ccc2c(c1)[nH]c(n2)NC(=O)C(CCC3CCCCC3)c4cccc(c4)Cl −8.0 ± 0.3 5.8 ± 0.2
75 EDJ-MED-c8e7a002-1 molecule COc1ccc2c(c1)onc2NC(=O)Cc3cccc(c3)Cl −7.9 ± 0.2 5.8 ± 0.1
76 JOH-UNI-3fc3434e-6 molecule c1ccc2c(c1)cncc2NC(=O)C(CC#N)c3cccc(c3)Cl −7.9 ± 0.1 5.8 ± 0.1
77 RUB-POS-1325a9ea-4 molecule Cc1ccc2cncc(c2c1)NC(=O)Cc3cccc(c3)Cl −7.94 ± 0.07 5.78 ± 0.05
78 EDJ-MED-00c1612e-1 molecule COc1ccc2cncc(c2c1)NC(=O)Cc3cccc(c3)Cl −7.93 ± 0.08 5.78 ± 0.06
79 JOH-UNI-a38a7bdd-1 molecule c1ccc2c(c1)cncc2N(C(=O)Cc3cccc(c3)Cl)C(=O)C(F)(F)F −7.9 ± 0.2 5.8 ± 0.1
80 NAU-LAT-4ce8bf23-2 molecule c1ccc2c(c1)cncc2N(CCC(=O)N)C(=O)Cc3cccc(c3)Cl −7.9 ± 0.2 5.8 ± 0.2
81 PET-UNK-1320d94d-10 molecule c1ccc2c(c1)cncc2NC(=O)[C@H](c3cccc(c3)Cl)NC(=O)[C@@H]4CCC[C@@H](O4)C(=O)N5CCCC5 −7.9 ± 0.3 5.7 ± 0.2
82 PET-UNK-ac320b15-10 molecule c1ccc2c(c1)cncc2NC(=O)[C@H](c3cccc(c3)Cl)NC(=O)[C@H]4CC[C@H](O4)C(=O)N5CCCC5 −7.9 ± 0.2 5.7 ± 0.1
83 ROB-UNI-daaf9793-3 molecule c1ccc2c(c1)CC(=CC2=O)NC(=O)Cc3cccc(c3)Cl −7.9 ± 0.1 5.73 ± 0.09
84 MAK-UNK-c749d764-22 molecule CC(CNCC1CCCO1)C(c2cccc(c2)Cl)C(=O)Nc3cncc4c3cccc4 −7.8 ± 0.1 5.7 ± 0.1
85 MAK-UNK-ffc90da7-4 molecule CC(CNCC1CCCO1)C(c2cccc(c2)Cl)C(=O)Nc3cncc4c3cccc4 −7.8 ± 0.2 5.7 ± 0.1
86 EDJ-MED-ee07cf00-13 molecule Cc1nc2n(n1)C[C@@H](CC2)C(=O)NC(c3cccc(c3)Cl)C(=O)Nc4cncc5c4cccc5 −7.8 ± 0.2 5.7 ± 0.1
87 PET-UNK-e8c7a26f-2 molecule C=CC(=O)N(c1cccnc1)C(=O)Cc2cccc(c2)Cl −7.8 ± 0.2 5.7 ± 0.1
88 PET-UNK-bbe8d7ff-1 molecule Cc1ccncc1N(CC=O)C(=O)Cc2cccc(c2)Cl −7.8 ± 0.2 5.7 ± 0.1
89 JOH-UNI-ee5ed7c8-7 molecule CN(c1cncc2c1cccc2)C(=O)C(CC#N)c3cccc(c3)Cl −7.8 ± 0.3 5.7 ± 0.2
90 EDJ-MED-cf4b0d25-3 molecule c1ccc2c(c1)cncc2NC(=O)C(c3cccc(c3)Cl)NC(=O)[C@@H]4CCCO4 −7.78 ± 0.07 5.67 ± 0.05
91 PET-UNK-1320d94d-22 molecule CN(C)C(=O)[C@H]1CC[C@H](O1)C(=O)N(C)[C@@H](c2cccc(c2)Cl)C(=O)Nc3cncc4c3cccc4 −7.8 ± 0.2 5.6 ± 0.1
92 JAN-GHE-5a013bed-6 molecule c1cc(cc(c1)Cl)CC(=O)Nc2cnns2 −7.8 ± 0.1 5.65 ± 0.09
93 RUB-POS-1325a9ea-14 molecule Cn1c2c(cncc2NC(=O)Cc3cccc(c3)Cl)cn1 −7.72 ± 0.08 5.62 ± 0.06
94 NAU-LAT-2fed8305-1 molecule CC(C)(c1cccc(c1)Cl)C(=O)Nc2cncc3c2cccc3 −7.71 ± 0.05 5.62 ± 0.03
95 JOH-UNI-3fc3434e-7 molecule CN(c1cncc2c1cccc2)C(=O)C(CC#N)c3cccc(c3)Cl −7.7 ± 0.2 5.6 ± 0.2
96 MIC-UNK-67d4a29a-4 molecule CN(c1cncc2c1c(ccc2)OC)C(=O)Cc3cccc(c3)Cl −7.7 ± 0.3 5.6 ± 0.2
97 MAT-POS-29385cc1-1 molecule COc1cc2c(cc1F)cncc2NC(=O)Cc3cccc(c3)Cl −7.7 ± 0.1 5.59 ± 0.10
98 PET-UNK-1320d94d-4 molecule c1ccc2c(c1)cncc2NC(=O)[C@H](c3cccc(c3)Cl)NC(=O)[C@@H]4CC[C@@H](O4)C(=O)N5CCOCC5 −7.6 ± 0.3 5.6 ± 0.2
99 JOH-UNI-3fc3434e-3 molecule c1cc(cc(c1)Cl)CC(=O)Nc2cncc3c2c(ccc3)CC(F)(F)F −7.6 ± 0.1 5.56 ± 0.10
100 MIC-UNK-5a93dd5f-2 molecule c1ccc2c(c1)cncc2NC(=O)C(c3cccc(c3)Cl)N4CC5CCCCC5C4 −7.6 ± 0.1 5.56 ± 0.10

Raw data

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Structures

Last updated 2021-08-18T07:55:07.929679+00:00
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