ArticleCellular microbiology2015
Inhibition of viral protein translation by indomethacin in vesicular stomatitis virus infection: role of eIF2α kinase PKR.
Article in Cellular microbiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 55 citations in OpenAlex.
- An open label randomized clinical trial of Indomethacin for mild and moderate hospitalised Covid-19 patients.Scientific reports · 2022Trial
- The potential role of indomethacin in COVID-19 management: A systematic review of therapeutic and mechanistic evidence.New microbes and new infections · 2026Review
- Antiviral activity of the non-steroidal anti-inflammatory drug indomethacin against respiratory syncytial virus.Virus research · 2026Article
- Review
- Assessing the Immunogenicity of Synthetic RNA Using Blood Cells.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Article
- Human coronaviruses activate and hijack the host transcription factor HSF1 to enhance viral replication.Cellular and molecular life sciences : CMLS · 2024Article
- Indomethacin inhibits human seasonal coronaviruses at late stages of viral replication in lung cells: Impact on virus-induced COX-2 expression.Journal of virus eradication · 2024Article
- Deciphering the Broad Antimicrobial Activity ofInternational journal of molecular sciences · 2023Article
- Molecular Basic of Pharmacotherapy of Cytokine Imbalance as a Component of Intervertebral Disc Degeneration Treatment.International journal of molecular sciences · 2023Review
- Indomethacin: Effect of Diffusionless Crystal Growth on Thermal Stability during Long-Term Storage.Molecules (Basel, Switzerland) · 2023Article
- The FDA-approved drug nitazoxanide is a potent inhibitor of human seasonal coronaviruses acting at postentry level: effect on the viral spike glycoprotein.Frontiers in microbiology · 2023Article
- Small molecules in the treatment of COVID-19.Signal transduction and targeted therapy · 2022Review
- Indomethacin: The Interplay between Structural Relaxation, Viscous Flow and Crystal Growth.Molecules (Basel, Switzerland) · 2022Article
- In-silico screening and in-vitro assay show the antiviral effect of Indomethacin against SARS-CoV-2.Computers in biology and medicine · 2022Article
- A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Management of Mild-to-Moderate Symptomatic COVID-19.Medical science monitor : international medical journal of experimental and clinical research · 2022Article
- Potential inhibitors of the main protease of SARS-CoV-2 and modulators of arachidonic acid pathway: Non-steroidal anti-inflammatory drugs against COVID-19.Computers in biology and medicine · 2021Article
- Review
- A novel function of African Swine Fever Virus pE66L in inhibition of host translation by the PKR/eIF2α pathway.Journal of virology · 2021Article
- Dynamic Changes in the Expression of Interferon-Stimulated Genes in Joints of SPF Chickens Infected With Avian Reovirus.Frontiers in veterinary science · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Indomethacin, a cyclooxygenase-1 and -2 inhibitor widely used in the clinic for its potent anti-inflammatory/analgesic properties, possesses antiviral activity against several viral pathogens; however, the mechanism of antiviral action remains elusive. We have recently shown that indomethacin activates the double-stranded RNA (dsRNA)-dependent protein kinase R (PKR) in human colon cancer cells. Because of the important role of PKR in the cellular defence response against viral infection, herein we investigated the effect of indomethacin on PKR activity during infection with the prototype rhabdovirus vesicular stomatitis virus. Indomethacin was found to activate PKR in an interferon- and dsRNA-independent manner, causing rapid (< 5 min) phosphorylation of eukaryotic initiation factor-2 α-subunit (eIF2α). These events resulted in shutting off viral protein translation and blocking viral replication (IC50 = 2 μM) while protecting host cells from virus-induced damage. Indomethacin did not affect eIF2α kinases PKR-like endoplasmic reticulum-resident protein kinase (PERK) and general control non-derepressible-2 (GCN2) kinase, and was unable to trigger eIF2α phosphorylation in the presence of PKR inhibitor 2-aminopurine. In addition, small-interfering RNA-mediated PKR gene silencing dampened the antiviral effect in indomethacin-treated cells. The results identify PKR as a critical target for the antiviral activity of indomethacin and indicate that eIF2α phosphorylation could be a key element in the broad spectrum antiviral activity of the drug.
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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.