ArticleAntiviral research2019
Small molecule grp94 inhibitors block dengue and Zika virus replication.
Article in Antiviral research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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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
32 citing papers in PubMed.
- Heat Shock Protein 90: From Molecular Chaperone Function to Therapeutic Targeting in Malignancies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Heat shock protein Gp96 (Grp94) in malaria: functional insights at the host-parasite interface and therapeutic perspectives.Frontiers in cell and developmental biology · 2026Review
- Coronaviral nsp6 hijacks ERAD machinery to facilitate lipolysis and supply membrane components for DMV growth.Nature communications · 2025Article
- Angiotensin-Converting Enzyme-2 (ACE2) Downregulation During Coronavirus Infection.Molecular biotechnology · 2025Review
- Exploiting host kinases to combat dengue virus infection and disease.Antiviral research · 2025Review
- A Novel Small-Molecule GRP94 Modulator Increases PCSK9 Secretion and Promotes LDLR Degradation.Life (Basel, Switzerland) · 2025Article
- Glucose-regulated protein 94 (Grp94/gp96) in viral pathogenesis: Insights into its role and therapeutic potentials.European journal of medicinal chemistry · 2025Review
- Advances in antiviral strategies targeting mosquito-borne viruses: cellular, viral, and immune-related approaches.Virology journal · 2025Review
- Discovery of Potent Degraders of the Dengue Virus Envelope Protein.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Multiple Mechanisms of Action of SulfodyneAntioxidants (Basel, Switzerland) · 2024Article
- Discovery of Potent Degraders of the Dengue Virus Envelope Protein.bioRxiv : the preprint server for biology · 2024Article
- Repurposing screen identifies novel candidates for broad-spectrum coronavirus antivirals and druggable host targets.Antimicrobial agents and chemotherapy · 2024Article
- Review
- Structural and functional complexity of HSP90 in cellular homeostasis and disease.Nature reviews. Molecular cell biology · 2023Review
- Unraveling the Mechanism of Epichaperome Modulation by Zelavespib: Biochemical Insights on Target Occupancy and Extended Residence Time at the Site of Action.Biomedicines · 2023Article
- Quinazolinone Compounds Have Potent Antiviral Activity against Zika and Dengue Virus.Journal of medicinal chemistry · 2023Article
- 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
- The biology and inhibition of glucose-regulated protein 94/gp96.Medicinal research reviews · 2022Review
- Viruses Hijack ERAD to Regulate Their Replication and Propagation.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
9 authors.
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Abstract
Two major flaviviruses, dengue virus (DENV) and Zika virus (ZIKV), cause severe health and economic burdens worldwide. Recently, genome-wide screenings have uncovered the importance of regulators of the Hrd1 ubiquitin ligase-mediated endoplasmic reticulum (ER)-associated degradation (ERAD) pathway for flavivirus replication in host cells. Here we report the identification of the compound Bardoxolone methyl (CDDO-me) as a potent inhibitor of the Hrd1 ubiquitin ligase-mediated ERAD, which possesses a broad-spectrum activity against both DENV and ZIKV. Cellular thermal shift assay (CETSA) suggested that CDDO-me binds to grp94, a key component of the Hrd1 pathway, at a low nanomolar concentration, whereas interaction was not detected with its paralog Hsp90. CDDO-me and the grp94 inhibitor PU-WS13 substantially suppressed DENV2 replication and the cytopathic effects caused by DENV and ZIKV infection. The antiviral activities of both compounds were demonstrated for all four DENV serotypes and four ZIKV strains in multiple human cell lines. This study defines grp94 as a crucial host factor for flavivirus replication and identified CDDO-me as a potent small molecule inhibitor of flavivirus infection. Inhibition of grp94 may contribute to the antiviral activity of CDDO-me. Further investigation of grp94 inhibitors may lead to a new class of broad-spectrum anti-flaviviral medications.
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