ArticleScientific reports2019
A small molecule inhibitor of ER-to-cytosol protein dislocation exhibits anti-dengue and anti-Zika virus activity.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- The role of ER-associated degradation and ER-phagy in health and disease.Signal transduction and targeted therapy · 2026Review
- A Novel Small-Molecule GRP94 Modulator Increases PCSK9 Secretion and Promotes LDLR Degradation.Life (Basel, Switzerland) · 2025Article
- Novel and repurposed antiviral molecules for arbovirus infections with epidemic Potential: A systematic review.New microbes and new infections · 2025Review
- Review
- Mechanisms of substrate processing during ER-associated protein degradation.Nature reviews. Molecular cell biology · 2023Review
- A quinolin-8-ol sub-millimolar inhibitor of UGGT, the ER glycoprotein folding quality control checkpoint.iScience · 2023Article
- Host E3 ligase Hrd1 ubiquitinates and degrades H protein of canine distemper virus to inhibit viral replication.Veterinary research · 2023Article
- Article
- 4-Phenyl-butyric Acid Inhibits Japanese Encephalitis Virus Replication via Inhibiting Endoplasmic Reticulum Stress Response.Viruses · 2023Article
- A small-molecule inhibitor and degrader of the RNF5 ubiquitin ligase.Molecular biology of the cell · 2022Article
- Viruses Hijack ERAD to Regulate Their Replication and Propagation.International journal of molecular sciences · 2022Review
- Stress-induced protein disaggregation in the endoplasmic reticulum catalysed by BiP.Nature communications · 2022Article
- Article
- Cell-Based High-Throughput Screening Protocol for Discovering Antiviral Inhibitors Against SARS-COV-2 Main Protease (3CLpro).Molecular biotechnology · 2021Article
- Role of Endoplasmic Reticulum-Associated Proteins in Flavivirus Replication and Assembly Complexes.Pathogens (Basel, Switzerland) · 2019Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Infection with flaviviruses, such as dengue virus (DENV) and the recently re-emerging Zika virus (ZIKV), represents an increasing global risk. Targeting essential host elements required for flavivirus replication represents an attractive approach for the discovery of antiviral agents. Previous studies have identified several components of the Hrd1 ubiquitin ligase-mediated endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, a cellular protein quality control process, as host factors crucial for DENV and ZIKV replication. Here, we report that CP26, a small molecule inhibitor of protein dislocation from the ER lumen to the cytosol, which is an essential step for ERAD, has broad-spectrum anti-flavivirus activity. CP26 targets the Hrd1 complex, inhibits ERAD, and induces ER stress. Ricin and cholera toxins are known to hijack the protein dislocation machinery to reach the cytosol, where they exert their cytotoxic effects. CP26 selectively inhibits the activity of cholera toxin but not that of ricin. CP26 exhibits a significant inhibitory activity against both DENV and ZIKV, providing substantial protection to the host cells against virus-induced cell death. This study identified a novel dislocation inhibitor, CP26, that shows potent anti-DENV and anti-ZIKV activity in cells. Furthermore, this study provides the first example of the targeting of host ER dislocation with small molecules to combat flavivirus infection.
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