ArticleVirology journal2023
Brequinar inhibits African swine fever virus replication in vitro by activating ferroptosis.
Article in Virology journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- Mechanistic insights and therapeutic advances in antiviral strategies against African swine fever virus.Acta pharmaceutica Sinica. B · 2026Review
- Host-pathogen interactions in African swine fever: From viral entry to systemic disease progression.Cell insight · 2026Review
- Recent progress in understanding ferroptosis mechanisms in infectious diseases.Frontiers in cellular and infection microbiology · 2026Review
- Thonningianin A disrupts pA104R-DNA binding and inhibits African swine fever virus replication.Emerging microbes & infections · 2025Article
- Review
- African swine fever virus hijacks host pyrimidine metabolism to promote viral replication.Journal of virology · 2025Article
- Metabolomic evidence of bovine leukemia virus regulation on ferroptosis in bovine mammary epithelial cells.Veterinary research communications · 2025Article
- A Practical Framework for ASFV Disinfectant Evaluation: Differentiating Cytopathic Effects from Cytotoxicity via Integrated Analytical Methods.Pathogens (Basel, Switzerland) · 2025Article
- The multifaceted role of ferroptosis in infection and injury and its nutritional regulation in pigs.Journal of animal science and biotechnology · 2025Review
- Exploring antiviral strategies to combat African swine fever.FEMS microbiology reviews · 2025Review
- Screening of host proteins interacting with the African swine fever virus outer membrane protein CD2v.Frontiers in microbiology · 2025Article
- TRIM21 Promotes Oxidative Stress and Ferroptosis through the SQSTM1-NRF2-KEAP1 Axis to Increase the Titers of H5N1 Highly Pathogenic Avian Influenza Virus.International journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAfrican swine fever virus (ASFV) is one of the most fatal swine etiological agents and has a huge economic impact on the global pork industry. Given that no effective vaccines or anti-ASFV drugs are available, there remains a pressing need for novel anti-ASFV drugs. This study aimed to investigate the anti-African swine fever virus (ASFV) activity of brequinar, a DHODH inhibitor.
methodsThe anti-ASFV activity of brequinar was investigated using IFA, HAD, HAD
resultsIn this study, brequinar was found to effectively inhibit ASFV replication ex vivo in porcine alveolar macrophages (PAMs) in a dose-dependent manner. In kinetic studies, brequinar was found to maintain ASFV inhibition from 24 to 72 hpi. Mechanistically, the time-of-addition assay showed that brequinar exerted anti-ASFV activity in all treatment modes, including pre-, co-, and post-treatment rather than directly killing ASFV particles. Notably, FerroOrange, Mito-FerroGreen, and Liperfluo staining experiments showed that brequinar increased the accumulation of intracellular iron, mitochondrial iron, and lipid peroxides, respectively. Furthermore, we also found that ferroptosis agonist cisplatin treatment inhibited ASFV replication in a dose-dependent manner and the inhibitory effect of brequinar on ASFV was partially reversed by the ferroptosis inhibitor ferrostatin-1, suggesting that brequinar activates ferroptosis to inhibit ASFV replication. Interestingly, exogenous uridine supplementation attenuated the anti-ASFV activity of brequinar, indicating that brequinar inhibits ASFV replication by inhibiting DHODH activity and the depletion of intracellular pyrimidine pools; however, the induction of ferroptosis by brequinar treatment was not reversed by exogenous uridine supplementation, suggesting that brequinar activation of ferroptosis is not related to the metabolic function of pyrimidines.
conclusionsOur data confirm that brequinar displays potent antiviral activity against ASFV in vitro and reveal the mechanism by which brequinar inhibits ASFV replication by activating ferroptosis, independent of inhibiting pyrimidine synthesis, providing novel targets for the development of anti-ASFV drugs.
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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.