Prophylactic and therapeutic itaconate treatment alleviates COVID-19-associated lung injury

ABSTRACT: Itaconate (ITA), an immunomodulatory metabolite with known anti-inflammatory properties, has underexplored therapeutic and prophylactic potential against coronavirus disease 2019 (COVID-19). Metabolomic analyses revealed that intranasal administration of a dNS1-RBD vaccine (a live-attenuated, cold-adapted influenza virus-based vaccine deficient in nonstructural protein 1 [NS1] and expressing the SARS-CoV-2 receptor binding domain (RBD)) upregulated ITA levels, prompting further exploration of its immunomodulatory role. This multiomics study investigates the therapeutic and prophylactic potential of ITA against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced acute lung injury (ALI) using an interanimal transmission hamster model that mimics the predominant natural route of SARS-CoV-2 infection. Both prophylactic and therapeutic ITA treatments significantly mitigated weight loss and improved lung pathology in infected hamsters. Transcriptional profiling demonstrated that ITA downregulated immune activation pathways while enhancing fatty acid β-oxidation (FAO)-related genes, correlating with reduced pro-inflammatory cytokine/chemokine release.

ORGANISM(S): Mesocricetus auratus

PROVIDER: GSE304799 | GEO | 2026/08/06

REPOSITORIES: GEO