In silico approach on mechanisms of action by funicone-like fungal metabolites in Canine Coronavirus infection

The alphacoronavirus canine coronavirus type II (CCoV-II) usually causes moderate enteritis in dogs, but its recombinational ability has led to the emergence of variants that can provoke serious diseases in dogs and humans. Since 2005, pantropic strains of CCoV have emerged, causing lethal multi-systemic disease, especially in young puppies. Subsequently, harmful novel CCoV strains causing acute respiratory illness have been isolated from humans in several countries [ 1 ]. Polyketides, funicone-like compounds, are a homogeneous group of fungal secondary metabolites that are potential drug candidates due to their valuable properties, including antibiotic, antiviral, cytotoxic, and insecticidal bioactivities [ 2 ]. We demonstrated that 3-O-methylfunicone (OMF), vermistatin (VER), and penisimplicissin (PEN) ([ Fig. 1 ]), produced by the fungus Talaromyces pinophilus , have antiviral activity against CCoV in canine fibrosarcoma cells (A72) [ 3 ] [ 4 ]. Indeed, these compounds significantly increased cell viability and also caused a substantial decline in virus yield and in the levels of viral nucleocapsid protein. Interestingly, during treatment, a cellular defense mechanism was revealed in the downregulation of aryl hydrocarbon receptor (AhR) signaling, which is affected by CCoV infection [ 5 ]. Fig. 1 Structure of 3- O -methylfunicone (OMF), vermistatin (VER), penisimplicissin (PEN), and CH223191 Here, we show a computational approach of Molecular Docking studies and structural modeling analysis. Using this approach, we investigated the molecular contacts involved in the stabilization of AhR-funicones complexes. The analyzed funicones interact with the same binding pocket recognized by the AhR inhibitor CH223191 ([ Fig. 1 ]), suggesting that they may be characterized by a similar recognition mechanism. Overall, these data suggest that funicones could represent potential innovative drugs, having AhR as a target for therapy against CoVs. Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany