What does this research mean for the field?

Cis-aconitate therapy significantly improves survival in influenza-infected mice by dual targeting viral polymerase and inflammatory signaling pathways. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.CHALLENGES_CONSENSUS.

What question did this study set out to answer?

The study aims to evaluate the efficacy of cis-aconitate as a treatment for influenza by targeting viral replication and inflammation.

February 19, 2026EMBO Molecular Medicine1 citationsOpen Access

Cis-aconitate therapy protects against influenza mortality by dual targeting of viral polymerase and ERK/AKT/NF-κB signaling

ACAdeline CezardUniversité de Tours DBDéborah Brea-DiakiteUniversité de Tours VVVirginie VasseurUniversité de Tours

Key Points

The study aims to evaluate the efficacy of cis-aconitate as a treatment for influenza by targeting viral replication and inflammation.
Evaluated cis-aconitate's effects on viral polymerase activity in vitro.
Tested efficacy across various influenza A and B strains.
Used ex vivo human airway and lung organotypic models for inflammation assessment.
Assessed therapeutic outcomes in a mouse model of influenza pneumonia.
Cis-aconitate reduced viral mRNA expression and protein synthesis.
Decreased inflammatory mediator secretion and disrupted inflammatory cascades.
Improved survival rates in the mouse model compared to controls.
Efficacy was demonstrated even at later stages of infection.

Abstract

Abstract The influenza virus poses a significant global health challenge, causing approximately 500,000 deaths annually. Its ability to evade antiviral treatments and vaccine-induced immunity underscores the need for novel therapeutic approaches. Our study identifies cis -aconitate ( cis -aco), a mitochondria-derived metabolite, as a potent dual-action agent against influenza, independently of its metabolic derivative, itaconate. Cis -aco impairs viral polymerase activity, resulting in decreased viral mRNA expression and protein synthesis, as observed for the influenza A/Scotland/20/74 (H3N2) strain. This antiviral effect was further confirmed across multiple influenza A and B strains, as well as in ex vivo human airway and lung organotypic models. Beyond its antiviral properties, cis- aco exhibits potent anti-inflammatory effects, disrupting key inflammatory cascades and reducing the secretion of inflammatory mediators. In a mouse model of influenza pneumonia, cis -aco mitigates viral replication, inflammation, and immune cell activation, significantly improving survival. Notably, its efficacy persists even when administered at later stages of infection, when oseltamivir/Tamiflu® is no longer effective. These findings position cis -aco as a promising influenza treatment, combining antiviral and anti-inflammatory benefits within a clinically relevant timeframe.

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