ArticleEMBO molecular medicine2024
Methotrimeprazine is a neuroprotective antiviral in JEV infection via adaptive ER stress and autophagy.
Article in EMBO molecular medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- c-Fos enhances influenza virus replication by stabilizing the M2 protein and promoting autophagosome accumulation.Journal of virology · 2026Article
- IP3R2-mediated inter-organelle calcium signaling suppresses melanosome degradation.PLoS biology · 2026Article
- STING is a key driver of Japanese encephalitis virus induced inflammatory response.Communications biology · 2026Article
- Downmodulation of cholesterol biosynthetic network governs activation of the innate immune response to Japanese encephalitis virus infection.Journal of virology · 2026Article
- Neuroinflammation and blood-brain barrier disruption in Japanese encephalitis virus infection: mechanisms, therapeutic targets, and intervention strategies.Archives of pharmacal research · 2026Review
- Endophilin mediated endocytosis and epidermal growth factor receptor govern Japanese encephalitis virus entry and infection in neuronal cells.PLoS pathogens · 2025Article
- Orthoflavivirus infection and the mTOR signaling pathway.Frontiers in microbiology · 2025Review
- Design, Synthesis, and Biological Evaluation of Novel Coumarin Analogs Targeted against SARS-CoV-2.Molecules (Basel, Switzerland) · 2024Article
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
Abstract
Japanese encephalitis virus (JEV) pathogenesis is driven by a combination of neuronal death and neuroinflammation. We tested 42 FDA-approved drugs that were shown to induce autophagy for antiviral effects. Four drugs were tested in the JE mouse model based on in vitro protective effects on neuronal cell death, inhibition of viral replication, and anti-inflammatory effects. The antipsychotic phenothiazines Methotrimeprazine (MTP) & Trifluoperazine showed a significant survival benefit with reduced virus titers in the brain, prevention of BBB breach, and inhibition of neuroinflammation. Both drugs were potent mTOR-independent autophagy flux inducers. MTP inhibited SERCA channel functioning, and induced an adaptive ER stress response in diverse cell types. Pharmacological rescue of ER stress blocked autophagy and antiviral effect. MTP did not alter translation of viral RNA, but exerted autophagy-dependent antiviral effect by inhibiting JEV replication complexes. Drug-induced autophagy resulted in reduced NLRP3 protein levels, and attenuation of inflammatory cytokine/chemokine release from infected microglial cells. Our study suggests that MTP exerts a combined antiviral and anti-inflammatory effect in JEV infection, and has therapeutic potential for JE treatment.
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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.