Discovery of New\n1,2,4-Triazole/1,3,4-Oxadiazole-Decorated\nQuinolinones as Agrochemical Alternatives for Controlling Viral Infection\nby Inhibiting the Viral Replication and Self-Assembly Process

Tobacco mosaic virus (TMV), a representative plant virus,\nis widely\nknown and causes severe crop losses worldwide. In order to ensure\nthe demand for crop and food security, the exploration of novel antiviral\nagents with outstanding activity and unique mechanisms of action is\nnecessary. Herein, 40 new azole–quinolinone molecules were\nelaborately designed and systematically evaluated for their anti-TMV\nactivity. Notably, compound <b>A</b><sub><b>21</b></sub> had significant therapeutic activity against TMV (EC<sub>50</sub> value = 200 μg/mL), which was superior to commercial ningnanmycin\n(280 μg/mL). Studies on the anti-TMV mechanism showed that compound <b>A</b><sub><b>21</b></sub> could suppress the expression\nlevel of important TMV genes and affect the assembly of TMV viral\nparticles by disrupting the self-assembly process of TMV coat protein\n(TMV-CP). In-depth antiviral behaviors were verified by molecular\ndocking, fluorescence titration analysis, and TMV assembly assays,\nsuggesting that compound <b>A</b><sub><b>21</b></sub> strongly\ninteracted with TMV coat protein through various interactions. Overall,\nthis promising work discloses a new paradigm for the exploitation\nof 2-quinolinone-based virucidal agents for hindering plant viral\ninfection through triggering versatile antiviral behavior.