Niclosamide SAR

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already on the radar, but I noticed the recently reported niclosamide hit with anti-MERS-CoV efficacies in Vero cells (not yet peer reviewed pre-print,

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,


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This is great digging Chris, I hadn’t read through that one yet. I’ve looked over your designs at , and quite a few are either purchasable, while the rest are quite easy to make and many in Enamine Real Space – so I think we definitely should prioritize Niclosamide since the SAR could be done easily and relatively cheaply.

I will follow up eventually with comments on that submission itself. Thanks again!

quick note: interesting that the paper lists the putative target as the ATP synthase

In case it’s useful, niclosamide is likely to be predominantly anionic under assay conditions.

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