Repurposing screen highlights broad-spectrum coronavirus antivirals and their host targets
Haid, S.; Matthaei, A.; Winkler, M.; Sake, S. M.; Gunesch, A. P.; Rueckert, J.; Vieyres, G.; Kuehl, D.; Nguyen, T.-T.; Lasswitz, L.; Zapatero, F.; Brogden, G.; Gerold, G.; Wiegmann, B.; Bilitewski, U.; Broenstrup, M.; Schulz, T.; Pietschmann, T.
Show abstract
Libraries composed of licensed drugs represent a vast repertoire of molecules modulating physiologic processes in humans, thus providing unique opportunities for discovery of host targeting antivirals. We interrogated the ReFRAME repurposing library with 12,993 molecules for broad-spectrum coronavirus antivirals and discovered 134 compounds inhibiting an alphacoronavirus, mapping to 59 molecular target categories. Dominant targets included the 5-hydroxytryptamine receptor and dopamine receptor and cyclin-dependent kinase inhibitors. Counter-screening with SARS-CoV-2 and validation in primary cells identified Phortress, an aryl hydrocarbon receptor (AHR) ligand, Bardoxolone and Omaveloxolone, two nuclear factor, erythroid 2 like 2 (NFE2L2) activators as inhibitors of both alpha- and betacoronaviruses. The landscape of coronavirus targeting molecules provides important information for the development of broad-spectrum antivirals reinforcing pandemic preparedness.
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