Inhibiting coronavirus replication by chemical ER stress, including SARS-CoV-2 and MERS-CoV

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 IRE1α 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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human) Middle East Respiratory Syndrome-related Coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 Chlorocebus Sabaeus

TISSUE(S): Permanent Cell Line Cell, Cell Culture

DISEASE(S): Severe Acute Respiratory Syndrome Coronavirus 2

SUBMITTER: Uwe Linne  

LAB HEAD: Uwe Linne

PROVIDER: PXD021222 | Pride | 2021-06-24

REPOSITORIES: Pride