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bioRxiv · 10.1101/2020.08.26.266304

Inhibiting coronavirus replication in cultured cells by chemical ER stress

Shaban, M. S.·Mueller, C.·Mayr-Buro, C.·Weiser, H.·Albert, B. V.·Weber, A.·Linne, U.·Hain, T.·Babayev, I.·Karl, N.·Hofmann, N.·Becker, S.·Herold, S.·Schmitz, M. L.·Ziebuhr, J.·Kracht, M.
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Abstract

Coronaviruses (CoVs) are important human pathogens for which no specific treatment is available. Here, we provide evidence that pharmacological reprogramming of ER stress pathways can be exploited to suppress CoV replication. We found that the ER stress inducer thapsigargin efficiently inhibits coronavirus (HCoV-229E, MERS-CoV, SARS-CoV-2) replication in different cell types, (partially) restores the virus-induced translational shut-down, and counteracts the CoV-mediated downregulation of IRE1 and the ER chaperone BiP. Proteome-wide data sets revealed specific pathways, protein networks and components that likely mediate the thapsigargin-induced antiviral state, including HERPUD1, an essential factor of ER quality control, and ER-associated protein degradation complexes. The data show that thapsigargin hits a central mechanism required for CoV replication, suggesting that thapsigargin (or derivatives thereof) may be developed into broad-spectrum anti-CoV drugs. One Sentence Summary / Running titleSuppression of coronavirus replication through thapsigargin-regulated ER stress, ERQC / ERAD and metabolic pathways

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Shaban, M. S., Mueller, C., Mayr-Buro, C., Weiser, H., Albert, B. V., Weber, A., Linne, U., Hain, T., Babayev, I., Karl, N., Hofmann, N., Becker, S., Herold, S., Schmitz, M. L., Ziebuhr, J., Kracht, M.. 2020-08-26. Inhibiting coronavirus replication in cultured cells by chemical ER stress. https://doi.org/10.1101/2020.08.26.266304

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