Brequinar Exerts Antiviral Effects Against Aquareovirus via Host Pyrimidine Metabolism Modulation.

Authors

Linyi Liu, Weijun Wu, Sen Han, Liqun Lu

Published in

Journal of fish diseases. Pages e70300. Oct 10, 2026. Epub Oct 10, 2026.

Abstract

Grass carp reovirus (GCRV) causes hemorrhagic disease in aquaculture, necessitating novel antivirals. Host-targeted broad-spectrum agents represent a promising approach. We evaluated Brequinar, a dihydroorotate dehydrogenase (DHODH) inhibitor in pyrimidine de novo synthesis, against GCRV in vitro and in vivo. In grass carp kidney (CIK) cells, Brequinar (0-50 μM) showed no cytotoxicity, dose-dependently alleviated cytopathic effect, reduced viral titers and suppressed VP5/VP7 expression. Antiviral efficacy was observed under pre-treatment, post-treatment and 48 h pre-treatment regimens, with post-infection administration showing stronger inhibition at moderate concentrations. In grass carp, Brequinar significantly reduced GCRV-II-induced mortality and tissue viral loads; post-infection dosing conferred better survival. Pharmacokinetic analysis demonstrated markedly greater systemic and tissue exposure following intraperitoneal administration than oral gavage, with peak concentrations reaching 1493.09 ng/mL in blood and 931.13 ng/mL in liver after intraperitoneal injection, compared with only 114.8 and 105.6 ng/mL, respectively, following oral administration. Transcriptomics demonstrated broad downregulation of pyrimidine metabolism genes, validated by sorbitol dehydrogenase (SORD) suppression. In a 30-day rare minnow model, Brequinar reduced viral loads after an initial rise, suggesting its potential application in reducing viral burden in virus-infected broodstock. Collectively, Brequinar exerts anti-GCRV activity by interfering with pyrimidine metabolism via DHODH inhibition and shows potential as a host-targeted antiviral strategy, with possible application in reducing viral burden in high-value broodstock in aquaculture.

PMID:
42856057
Bibliographic data and abstract were imported from PubMed on 10 Oct 2026.

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