Ipflufenoquin, Novel Dihydroorotate Dehydrogenase Inhibitor: Efficacy Against Strawberry Diseases and Docking Simulations via AlphaFold2 and Autodock Vina

Abstract

In 2023, fungal diseases, including Botrytis cinerea (gray mold), were isolated from various strawberry fields in Korea. Ipflufenoquin, a novel class 2 dihydroorotate dehydrogenase (DHODH) inhibitor, was applied to plant pathogenic fungal species. EC50 values indicated that ipflufenoquin achieved high sensitivity in B. cinerea while maintaining broad-spectrum activity against other fungi. Fruit and greenhouse trials confirmed its robust efficacy in gray mold diseases, including those resistant to conventional fungicides like pyraclostrobin, fluxapyroxad, and benomyl. However, the ipflufenoquin application was less effective against fungal pathogens like blossom blight and Rhizopus rot, causing shifts in the fungal community and allowing less sensitive species to emerge. Structural prediction using Alphafold2 and molecular docking simulation showed ipflufenoquin was bound to the quinone binding tunnel in DHODH and highlighted the correlation between protein-ligand binding affinity and fungicide susceptibility, with species showing higher affinities being more sensitive. This study is the first to report sensitivity of strawberry fungal species to ipflufenoquin, and this fungicide is recommended in strawberry farms against gray mold disease. Additionally, we conducted in silico predictions of fungicide sensitivity across various plant pathogenic fungi using Alphafod2 and Autodock Vina. This establishes a foundation for future computational analyses to predict the effectiveness of fungicides, offering important baseline data to enhance fungicide management strategies.