Antiviral activity and mechanisms of action of atropine, rutin, and hypoxanthine against tomato Brown rugose fruit virus

Plant viral diseases cause considerable damage to the agricultural industry and are difficult to control. Recently, botanical biopesticides that are environmentally friendly, safe for non-target organisms, and not prone to developing drug resistance have shown great potential as antiviral agents. In the present study a screening of natural products with antiviral potential was conducted, and three compounds - atropine, rutin, and hypoxanthine - were identified to possess anti-tomato brown rugose fruit virus (ToBRFV) activity. Further, the modes of action of these compounds were investigated. The results of the bioassay revealed that atropine, rutin and hypoxanthine were effective at concentrations of 50, 100 and 150 μg mL^-1 in inactivating, inhibiting proliferation and protecting against ToBRFV when combined with atropine and rutin. As the concentration of compounds increased, their antiviral properties were found to be enhanced. These compounds were found to reduce the expression of the coat protein and the replicase genes of ToBRFV. Atropine and rutin, in particular, demonstrated substantial anti-ToBRFV effects with diverse modes of action when used alone or in combination. Hypoxanthine demonstrated a comparatively weaker antiviral effect than the other two compounds, and when combined with the latter, the antiviral activity of the other compounds was also reduced to a certain extent. These results provided key proof that these compounds may represent a promising source of novel antiviral agents for agricultural use.