Discovery of phosphonate derivatives containing different substituted 1,2,3‐triazole motif as promising tobacco mosaic virus (TMV) helicase inhibitors for controlling plant viral diseases

The discovery and identification of targets is of far-reaching significance for developing novel pesticide candidates and increasing the probability of success. To explore and identify highly effective tobacco mosaic virus (TMV) helicase-targeted lead structures, a series of novel phosphonate derivatives containing a 1,2,3-triazole motif were rationally engineered and their antiviral activity was assessed.Bioassay results showed that the optimized B17 exhibited more potent curative activity (EC50 = 271.5 μg mL-1 ) against TMV in vivo, which was superior to that of commercial Ribavirin (EC50 = 689.3 μg mL-1 ). B17 presented a stronger binding capacity through binding analysis with helicase, affording a corresponding value of 12.7 μM. Enzyme activity assay showed B17 exhibited excellent inhibitory activity on TMV helicase (39.2% at 300 μM). Furthermore, molecular docking simulations demonstrated that B17 displayed strong hydrogen-bond interactions (2.1, 2.1, 2.2, and 3.2 Å) with Ala-33, Gly-10, Gly-8, and Glu-217 of TMV helicase. Encouragingly, transmission electron microscopy analysis revealed that B17 could remarkably disrupt surface morphology and inhibit TMV proliferation. Additionally, these compounds also displayed potential anti-CMV (cucumber mosaic virus) and antipathogens (Xanthomonas oryzae pv. oryzae and Xanthomonas axonopodis pv. citri) by expanding their applications in agriculture.Current research demonstrated that B17 could be considered as a potential antiviral agent alternative though targeting TMV helicase. © 2023 Society of Chemical Industry.