Dear PostEra COVID project organisers,
Probably already on the radar, but I noticed the recently reported niclosamide hit with anti-MERS-CoV efficacies in Vero cells (not yet peer reviewed pre-print, https://www.biorxiv.org/content/10.1101/2020.02.25.965582v2)
Tempting to hypothesise a binding mode for the the N-phenylbenzamide scaffold of Niclosamide similar to e.g. the benzamide (X_0678) and (di)phenylurea (X_0434) scaffolds.
Obviously early days as the work still has to be peer reviewed, there is not information on the actual mode of action and/or protein target. Furthermore appreciating that recognising simple substructures between hits and assuming they bind in a similar manner can be rather deceiving.
Desipte these and other caveats perhaps nevertheless some suggestions to e.g.:
- Consider niclosamide for X-ray crystallography by Frank von Delft/Diamond Lightsource team
- Explore simple SAR around the putative niclosamide hit (see some of the designs proposed under CHR-SOS-709)
as this can be helpful to provide more confidence in this preliminary binding mode hypothesis that niclosamide may (also) bind the protease target and to help prioritise/customise/extend the scope in subsequent iterative ligand design rounds.
Many thanks for your feedback,
Chris