Submission Details
Molecule(s):
CC(=O)NS(=O)(=O)c1ccc(-c2cnc(N3CCOCC3)c3nc(COc4ccc5ccccc5n4)cn23)cc1
CNC(=O)Nc1sc2ccccc2c1C(=O)N1CCC(N2CCCC3(C2)C(=O)N2CCCCN2C3=O)CC1
O=C(Nc1ccc(F)c(F)c1C(=O)N1CCC1)c1nc(C2CC2)cnc1Nc1cncnc1
Cc1ccc2cc(-c3n[nH]c4ccc(NS(=O)(=O)c5cccc(F)c5)cc34)[nH]c2c1
Design Rationale:
A rational structure-based approach to select screening compounds was investigated. Therefore, similar binding sites for COVID-19 main protease were searched (using ProBis), and the active compounds for the similar proteins were collected from ChEMBL. Furthermore, due to time-constraints, the focused library was filtered to keep the compounds having some resemblance with the 22 non-covalent fragments (using MCS). A representative set of three structures, Mpro-x0387, Mpro-x0946, Mpro-x0967, were then chosen to run multiple dockings with the filtered library using the docking program smina. Based on the docking scores, tox criteria (trying to avoid respiratory toxicity using estimations from eMolTox webserver) and after visual inspection these compounds were selected. ChEMBL IDs: CHEMBL3937948, CHEMBL2059095, CHEMBL3690047, CHEMBL1684519 Note that similar molecules are available in Enamine REAL, such a selection could be added here later (time restriction for now). More information - and more compounds if needed - can be found in our github repo: https://github.com/volkamerlab/covid19-SBapproach