ArticlePLoS pathogens2021
Manipulation of the unfolded protein response: A pharmacological strategy against coronavirus infection.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
57 citing papers in PubMed, 94 citations in OpenAlex.
- IRE1α Is Associated with Host Lipid Biosynthesis During Human Coronavirus OC43 Infection.Viruses · 2026Article
- RepurNet: A network medicine framework for systematic drug repurposing and disease vulnerability discovery.iScience · 2026Article
- RNF26 bridges ER stress and autophagy in the clearance of MERS envelope protein.Virologica Sinica · 2026Article
- A stable subgenomic reporter coronavirus enables transcriptional profiling of bystander cells.The Journal of general virology · 2026Article
- Chemical modulation of the unfolded protein response reveals an antiviral role for the PERK pathway in human coronavirus 229E infection.RSC chemical biology · 2026Article
- Targeting the UPR with Small Molecules: Emerging Strategies for Immune Regulation.Molecules (Basel, Switzerland) · 2026Review
- SARS-CoV-2 ORF8: an accessory protein at the interface of immune evasion and inflammation.Frontiers in immunology · 2026Review
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- The glycoprotein quality control factor Malectin promotes coronavirus replication and viral protein biogenesis.bioRxiv : the preprint server for biology · 2025Article
- Understanding the mechanisms of mitochondrial rewiring during viral infections.The Journal of general virology · 2025Review
- Human protein interaction networks of ancestral and variant SARS-CoV-2 in organ-specific cells and bodily fluids.Nature communications · 2025Article
- Subcellular localization of SARS-CoV-2 E and 3a proteins along the secretory pathway.Journal of molecular histology · 2025Article
- Article
- Acute COVID-19 and LongCOVID syndrome - molecular implications for therapeutic strategies - review.Frontiers in immunology · 2025Review
- Spring viraemia of carp virus modulates the time-dependent unfolded protein response to facilitate viral replication.Frontiers in immunology · 2025Article
- Single-cell gene regulatory network analysis for mixed cell populations.Quantitative biology (Beijing, China) · 2024Article
- Morbillivirus Canis Infection Induces Activation of Three Branches of Unfolded Protein Response, MAPK and Apoptosis.Viruses · 2024Article
- Zika viruses encode 5' upstream open reading frames affecting infection of human brain cells.Nature communications · 2024Article
- Activation of alveolar epithelial ER stress by β-coronavirus infection disrupts surfactant homeostasis in mice: implications for COVID-19 respiratory failure.American journal of physiology. Lung cellular and molecular physiology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
Coronavirus infection induces the unfolded protein response (UPR), a cellular signalling pathway composed of three branches, triggered by unfolded proteins in the endoplasmic reticulum (ER) due to high ER load. We have used RNA sequencing and ribosome profiling to investigate holistically the transcriptional and translational response to cellular infection by murine hepatitis virus (MHV), often used as a model for the Betacoronavirus genus to which the recently emerged SARS-CoV-2 also belongs. We found the UPR to be amongst the most significantly up-regulated pathways in response to MHV infection. To confirm and extend these observations, we show experimentally the induction of all three branches of the UPR in both MHV- and SARS-CoV-2-infected cells. Over-expression of the SARS-CoV-2 ORF8 or S proteins alone is itself sufficient to induce the UPR. Remarkably, pharmacological inhibition of the UPR greatly reduced the replication of both MHV and SARS-CoV-2, revealing the importance of this pathway for successful coronavirus replication. This was particularly striking when both IRE1α and ATF6 branches of the UPR were inhibited, reducing SARS-CoV-2 virion release (~1,000-fold). Together, these data highlight the UPR as a promising antiviral target to combat coronavirus infection.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.