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..
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Preprint| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
bioRxiv.org - (2021) vom: 16. Juli Zur Gesamtaufnahme - year:2021 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Haid, Sibylle [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2021.07.14.452343 |
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| PPN (Katalog-ID): |
XBI03220339X |
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| 520 | |a 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. | ||
| 700 | 1 | |a Matthaei, Alina |e verfasserin |4 aut | |
| 700 | 1 | |a Winkler, Melina |e verfasserin |4 aut | |
| 700 | 1 | |a Sake, Svenja M. |e verfasserin |4 aut | |
| 700 | 1 | |a Gunesch, Antonia P. |e verfasserin |4 aut | |
| 700 | 1 | |a Rückert, Jessica |e verfasserin |4 aut | |
| 700 | 1 | |a Vieyres, Gabrielle |e verfasserin |4 aut | |
| 700 | 1 | |a Kühl, David |e verfasserin |4 aut | |
| 700 | 1 | |a Nguyen, Tu-Trinh |e verfasserin |4 aut | |
| 700 | 1 | |a Lasswitz, Lisa |e verfasserin |4 aut | |
| 700 | 1 | |a Zapatero, Francisco |e verfasserin |4 aut | |
| 700 | 1 | |a Brogden, Graham |e verfasserin |4 aut | |
| 700 | 1 | |a Gerold, Gisa |e verfasserin |4 aut | |
| 700 | 1 | |a Wiegmann, Bettina |e verfasserin |4 aut | |
| 700 | 1 | |a Bilitewski, Ursula |e verfasserin |4 aut | |
| 700 | 1 | |a Brönstrup, Mark |e verfasserin |4 aut | |
| 700 | 1 | |a Schulz, Thomas F. |e verfasserin |4 aut | |
| 700 | 1 | |a Pietschmann, Thomas |e verfasserin |4 aut | |
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