Submission Details
Molecule(s):
CCc1[nH]n(-c2cccc(Cl)c2)c(=O)c1C1=C(N2C=CCC=C2)C(=O)N(c2cccc(C)c2)C1=O
CC(=O)N1CCCc2cc(NCc3ccc(F)cc3Cl)ccc21
Design Rationale:
These are two out of the 12 compounds, identified as most promising in the recent 687-million virtual screening for the SARS-CoV-2 main protease inhibitors by Fischer et al. [10.26434/chemrxiv.11923239]. Along with high affinity to the target active site, they also showed low affinities to 16 off-target proteins. We have additionally assessed affinities of these 12 compounds to the SARS-CoV-2 main protease outer surface because we have recently found, that high affinity to the protein surface can significantly affect ligands activities toward proteins with open active sites [our manuscript is currently under consideration in Chemical Science]. We have found, that these compounds (CP-5 and CP-7 in the original work) have very low affinities to the protein surface, which makes them the best performers using the method we developed for targets with open active sites. We, therefore, expect them to be the most active compound among the 12 identified by Fischer et al. [10.26434/chemrxiv.11923239].
Other Notes:
I did not find how to submit without choosing Fragment ids, nor how to look at more than seven Fragments in the viewer. So I have just selected an arbitrary fragment.