Submission Details
Molecule(s):
Cc1cccc(C)c1OCC(=O)N[C@@H](Cc1ccccc1)[C@@H](O)C[C@H](Cc1ccccc1)NC(=O)[C@H](C(C)C)N1CCCNC1=O
CC(C)c1nc(CN(C)C(=O)N[C@H](C(=O)N[C@@H](Cc2ccccc2)C[C@H](O)[C@H](Cc2ccccc2)NC(=O)OCc2cncs2)C(C)C)cs1
Cc1cccc(C)c1OCC(=O)NCCc1ccccc1
O=C(COc1ccccc1)NCCc1ccccc1
CCC(C)NC(=O)COc1c(C)cccc1C
CCCC(=O)NC(CC)Cc1ccccc1
CCCCCC(C)NC(=O)COc1ccccc1
CCCC(C)NC(=O)COc1ccccc1
CCCNC(=O)C(C)NC(=O)N(C)Cc1csc(C)n1
Design Rationale:
Lopinavir/ritonavir and similar substructures from catalog. The combination lopinavir/ritonavir is currently tested against COVID-19, but "no benefit was observed with lopinavir–ritonavir treatment beyond standard care". (doi: 10.1056/NEJMoa2001282) Reportedly, lopinavir has only mid-micromolar activity against SARS protease, ritonavir above 50 microM. (doi: 10.12688/f1000research.22457.1; doi: 10.1073/pnas.0403596101) However, there is no crystal structure of the 2019-nCoV main protease with either of these two drugs that could clarify their potential for optimization against this target. Thus, I suggest lopinavir, ritonavir, and reasonably similar substructures available from catalog for soaking. Procedure in KNIME: 1) search all substructures of lopinavir and ritonavir in MolPort 2) remove all redundant compounds and compounds with similarity < 0.5 (datawarrior SkelPheres) to either of the queries 3) remove all compounds void of a ring or containing amides (as substructures of amides) Selection not based on or compared to fragment hits; x0072 selected as dummy.
Other Notes:
MolPort-003-848-410 MolPort-000-883-877 MolPort-001-572-165 MolPort-000-418-325 MolPort-002-271-944 MolPort-001-959-578 MolPort-019-079-691 MolPort-001-527-709 MolPort-020-128-938