Repurposing screen highlights broad-spectrum coronavirus antivirals and their host targets

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.

High throughput screening identifies broad-spectrum Coronavirus entry inhibitors

“…Despite numerous efforts, few novel and efficient antivirals were identified [42][43][44][45] . Furthermore, while numerous in silico and in vitro HTS approaches targeting viral entry or viral replication have been developed, efforts specifically dedicated to the identification of broad-spectrum CoV antivirals through HTS have been sparse 46,47 .…”