Montanine, an Amaryllidaceae alkaloid, has demonstrated superior antiviral activity against dengue virus (DENV), SARS-CoV-2, vesicular stomatitis Indiana virus (VSV-G), and vesicular stomatitis virus pseudotyped with Ebola virus glycoprotein (VSV-ZGP), outperforming other antiviral alkaloids tested, including lycorine, narciclasine, tetracetylnarciclasine, and pancracine. We further showed that montanine inhibits translation in mammalian cells, as evidenced by a puromycin incorporation assay. Cryo-EM analysis revealed that montanine binds to the peptidyl transferase center of the human ribosome. A chemical genomics survey indicated that the knockdown of the GCN1 complex, which senses ribosome collisions and triggers the translation quality control process, increased the cytotoxicity of montanine while reducing viral infectivity. Together, these results suggest that the antiviral activity of montanine is closely linked to its impact on translational elongation and GCN1-related stress responses, underscoring the potential of translation control as a targeted mode for RNA virus therapeutics.
Magnetoencephalography reveals adaptive neural reorganization maintaining lexical-semantic proficiency in healthy aging
Although semantic cognition remains behaviorally stable with age, neuroimaging studies report age-related alterations in response to semantic context. We aimed to reconcile these inconsistent findings