MNS induces antiviral protection and suppresses inflammation

Abstract

BackgroundIdentifying safe and broad-spectrum antiviral and anti-inflammatory agents remains an urgent need in infectious and inflammatory diseases. Here, we demonstrated that MNS (NSC170724), a small-molecule nitrovinyl benzodioxole, enhanced antiviral defense while limiting excessive inflammation. MethodsThe antiviral activity of MNS was evaluated in multiple cell lines and mouse infection models across DNA and RNA viruses. Virus-induced and LPS-induced inflammatory responses were assessed using RT-qPCR, ELISA and western blotting. Bulk RNA-seq and ATAC-seq were performed to define transcriptional and epigenetic mechanisms. ResultsMNS significantly suppressed viral infection in vitro and improved survival in four lethal viral infection models, accompanied by reduced viral loads and attenuated tissue injury. MNS also diminished virus-triggered and LPS-triggered inflammatory cytokine production in macrophages and multiple mouse organs, and protected mice from LPS-induced endotoxic lethality. Multi-omics profiling showed that MNS broadly repressed LPS-induced inflammatory transcriptional programs and reversed chromatin accessibility gains across promoters and transcription start sites. Joint analysis of RNA-seq and ATAC-seq data demonstrated consistent downregulation of pivotal inflammatory pathways, such as NF-{kappa}B, Toll-like receptor, and TNF signaling. ConclusionsWith potent activity against viral replication and inflammation in cellular and animal models, MNS emerges as a promising candidate for the treatment of viral infections and hyperinflammatory conditions.