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Coronavirus uses endoplasmic reticulum (ER) as a site for synthesis and processing of viral proteins. During HCoV infection, viral structural proteins, in particular the S glycoprotein, are produced in massive amounts saturating the ER folding capacity. Thus, unfolded proteins accumulate in the ER triggering an unfolded protein response (UPR). The UPR is mediated by three ER-resident transmembrane proteins PKR-like ER kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring enzyme 1 (IRE-1) and alleviates the stress both by globally attenuating translation and by up-regulating genes facilitating protein folding and degradation.

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2025-11-26
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