ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026
Targeting β2-Adrenergic Receptor Stability With Lycorine Reveals a Host-Directed Pathway for Antiviral Defense Against Poxviruses.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Psychological stress is a pervasive yet poorly understood modulator of infectious disease outcomes. Here, we report a mechanistic link between chronic stress and severe viral pathogenesis, identifying the β2-adrenergic receptor (β2-AR) as a critical host factor and therapeutic target. Using a model of chronic restraint stress and cowpox virus (CPXV) infection, we demonstrate that psychological stress significantly exacerbates disease severity and mortality. This increased susceptibility is driven by autophagy-mediated downregulation of β2-AR, a process that is recapitulated during viral infection. Accordingly, genetic loss-of-function and pharmacological approaches established β2-AR as a critical host protective factor that suppresses CPXV replication. Leveraging this pathway, we identify the natural alkaloid lycorine as a novel β2-AR-stabilizing ligand that rescues the receptor from degradation. Lycorine exhibits potent antiviral activity by suppressing post-entry viral replication. In vivo, lycorine reduced viral burden and tissue pathology and improved survival following CPXV infection, and these protective effects required cluster of differentiation 8-positive (CD8
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