Roquefortine C isolated from a quail feces-derived fungus exhibits aryl hydrocarbon receptor antagonistic and broad-spectrum antiviral activities.

Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, regulates the metabolism of exogenous compounds. Pharmacological inhibition of AhR reduces lipid droplet (LD) accumulation and suppresses hepatitis C virus (HCV) proliferation. Recent evidence implicates AhR in the propagation of viruses such as herpes simplex virus type 1 (HSV-1), making it a host factor regulating the proliferation of diverse viruses and an attractive target for broad-spectrum antivirals. To identify AhR ligands with antiviral activity, we screened secondary metabolites derived from fungi isolated from various animals. We identified roquefortine C, an indole alkaloid obtained from quail-derived fungi, as an AhR antagonist. Roquefortine C suppressed LD formation and HCV production in human hepatoma cells. Additionally, it showed anti-HSV-1 and anti-pseudorabies virus (PRV) activities. Notably, our study demonstrated the relationship between AhR and PRV for the first time. AhR ligands could represent potential lead compounds with broad-spectrum antiviral properties.