tetano
Editor, Senior Moderator
EMBO Mol Med
. 2026 Feb 16.
doi: 10.1038/s44321-026-00379-8. Online ahead of print.
Cis-aconitate therapy protects against influenza mortality by dual targeting of viral polymerase and ERK/AKT/NF-κB signaling
Adeline Cezard[SUP] 1 2 [/SUP], Déborah Brea-Diakite[SUP] 1 2 [/SUP], Virginie Vasseur[SUP] 1 2 [/SUP], Alan Wacquiez[SUP] 1 2 [/SUP], Loic Gonzalez[SUP] 1 2 [/SUP], Ronan Le Goffic[SUP] 3 [/SUP], Bruno Da Costa[SUP] 3 [/SUP], Ambre Tinard[SUP] 1 2 [/SUP], Delphine Fouquenet[SUP] 1 2 [/SUP], Séverine Heumel[SUP] 4 [/SUP], Arnaud Machelart[SUP] 4 [/SUP], Eik Hoffmann[SUP] 4 [/SUP], Priscille Brodin[SUP] 4 [/SUP], François Trottein[SUP] 4 [/SUP], Cyrille Mathieu[SUP] 5 [/SUP], Lola Canus[SUP] 5 [/SUP], Florentine Jacolin[SUP] 5 [/SUP], Pierre-Olivier Vidalain[SUP] 5 [/SUP], Laure Perrin-Cocon[SUP] 5 [/SUP], Vincent Lotteau[SUP] 5 [/SUP], Julien Burlaud-Gaillard[SUP] 6 [/SUP], Dominique Tertigas[SUP] 7 [/SUP], Michael G Surette[SUP] 8 [/SUP], Antoine Legras[SUP] 2 9 [/SUP], Damien Sizaret[SUP] 10 [/SUP], Thomas Baranek[SUP] 1 2 [/SUP], Christophe Paget[SUP] 1 2 [/SUP], Antoine Guillon[SUP] 1 2 11 [/SUP], Mustapha Si-Tahar[SUP] 12 13 [/SUP]
Affiliations
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.
Keywords: Anti-inflammatory; Antiviral; Influenza Virus; Pneumonia; Therapy.
. 2026 Feb 16.
doi: 10.1038/s44321-026-00379-8. Online ahead of print.
Cis-aconitate therapy protects against influenza mortality by dual targeting of viral polymerase and ERK/AKT/NF-κB signaling
Adeline Cezard[SUP] 1 2 [/SUP], Déborah Brea-Diakite[SUP] 1 2 [/SUP], Virginie Vasseur[SUP] 1 2 [/SUP], Alan Wacquiez[SUP] 1 2 [/SUP], Loic Gonzalez[SUP] 1 2 [/SUP], Ronan Le Goffic[SUP] 3 [/SUP], Bruno Da Costa[SUP] 3 [/SUP], Ambre Tinard[SUP] 1 2 [/SUP], Delphine Fouquenet[SUP] 1 2 [/SUP], Séverine Heumel[SUP] 4 [/SUP], Arnaud Machelart[SUP] 4 [/SUP], Eik Hoffmann[SUP] 4 [/SUP], Priscille Brodin[SUP] 4 [/SUP], François Trottein[SUP] 4 [/SUP], Cyrille Mathieu[SUP] 5 [/SUP], Lola Canus[SUP] 5 [/SUP], Florentine Jacolin[SUP] 5 [/SUP], Pierre-Olivier Vidalain[SUP] 5 [/SUP], Laure Perrin-Cocon[SUP] 5 [/SUP], Vincent Lotteau[SUP] 5 [/SUP], Julien Burlaud-Gaillard[SUP] 6 [/SUP], Dominique Tertigas[SUP] 7 [/SUP], Michael G Surette[SUP] 8 [/SUP], Antoine Legras[SUP] 2 9 [/SUP], Damien Sizaret[SUP] 10 [/SUP], Thomas Baranek[SUP] 1 2 [/SUP], Christophe Paget[SUP] 1 2 [/SUP], Antoine Guillon[SUP] 1 2 11 [/SUP], Mustapha Si-Tahar[SUP] 12 13 [/SUP]
Affiliations
- PMID: 41699259
- DOI: 10.1038/s44321-026-00379-8
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.
Keywords: Anti-inflammatory; Antiviral; Influenza Virus; Pneumonia; Therapy.