Submission Details

Design Rationale:

We used a structure-based fragment growing approach for building on the complexes of different fragments bound to the virus main protease available from DiamondX. As starting point in this submission, fragment Mpro-x0967 was chosen based on its size, it being found as match in our focused library (molecules binding to similar proteins to the virus protease) and its good estimated affinity using BioSolveIT's SeeSAR software. SeeSAR was then used to grow (Recore) the fragment choosing a bond towards the bromide tail. To guarantee synthetic accessibility, similar compounds within Enamine REAL space were searched using FTrees, based on the most promising compounds (estimated affinity and visual inspection). The so found compounds (no duplicates in current postera submissions, 31.03.2020) were clustered to find a diverse subset and the remaining compounds were redocked using SeeSAR. Based on the fit and the estimated binding affinity (and no tox. predictions (CPs) in eMolTox webserver), the five molecules were selected. More information - and more compounds if needed - can be found in our github repo: https://github.com/volkamerlab/covid19-SBapproach

Inspired By: