Discovery of novel antiviral and antifungal agents based on flavonoid derivatives

In response to the severe threat posed by plant viral and fungicidal diseases to global agricultural production and the limitations of existing control strategies, this study aims to develop novel antiviral and fungicidal agents. Using the natural flavonoid chrysin as a lead compound, a series of structurally novel flavonoid derivatives were designed and synthesized, and their antiviral and antifungal activities were systematically evaluated. Bioassay results indicated compounds 4 L (56 %), 4Y(57 %), 4AE (58 %), and 4AF (61 %) had a greater inactive effect than the positive control ningnanmycin (55 %). Mechanistic studies revealed that the highly active compound 4AF suppresses viral particle assembly by binding to the TMV-CP, inducing prominent aggregation and structural fusio. Molecular docking simulations further demonstrated that stable hydrogen bond interactions exist between this class of compounds and the TMV-CP, providing preliminary elucidation of the underlying molecular mechanism. Additionally, multiple compounds showed significant inhibition against Physalospora piricola and Rhizoctonia cerealis. Compounds 4G, 4I, 4 J, and 4 N inhibited Physalospora piricola by over 95 %, and compound 4 N inhibited Rhizoctonia cerealis by 88 %. This study advances chrysin derivatives for integrated plant disease control.