Background: 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.
Results: 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.
Conclusion: Current research demonstrated that B17 could be considered as a potential antiviral agent alternative though targeting TMV helicase. © 2023 Society of Chemical Industry.
Keywords: 1,2,3-triazole; antiviral activity; helicase; molecular docking; phosphonates.
© 2023 Society of Chemical Industry.