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发现吡啶并[1,2-α]嘧啶酮杂环化合物作为防治马铃薯 Y 病毒的潜在控制剂。

Discovery of Pyrido[1,2-α] Pyrimidinone Mesoionic Compounds as Potential Control Agents Against Potato Virus Y.

机构信息

State Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Huaxi, Guiyang 550025, China.

Guizhou Institute of Soil and Fertilizer/Agricultural Resources and Environment, Guizhou Academy of Agricultural Sciences, Huaxi, Guiyang 550025, PR China.

出版信息

J Agric Food Chem. 2024 Jun 12;72(23):12925-12934. doi: 10.1021/acs.jafc.3c09867. Epub 2024 May 29.

DOI:10.1021/acs.jafc.3c09867
PMID:38809684
Abstract

Potato virus Y (PVY) relies on aphids and tubers to spread in the field and causes serious economic losses in the potato industry. Here, we found that pyrido[1,2-α] pyrimidinone mesoionic compounds with insecticidal activity against aphids possessed a good inhibitory effect on PVY. Among them, compound had the best inhibitory activity against PVY (EC = 104 μg/mL), even superior to that of ningnanmycin (125 μg/mL). The fluorescence and qPCR results confirmed that compound could inhibit the proliferation of PVY in . Preliminary experiments on the mechanism of action indicated that compound had good binding affinity with the coat protein (CP), which plays an essential role in aphid-PVY interactions. Molecular docking revealed that compound could bind to the pocket of CP formed by Ser52, Glu204, and Arg208. Compound had substantially lower binding affinity () values with CP (219 μM), CP (231 μM), and CP (189 μM) than those with CP (5.80 μM). A luciferase assay confirmed that mutating Ser52, Glu204, and Arg208 significantly affected the expression level of CP and further reduced virus proliferation. Therefore, the broad-spectrum activity of compound provides a unique strategy for the prevention and treatment of PVY.

摘要

马铃薯 Y 病毒(PVY)依靠蚜虫和块茎在田间传播,给马铃薯产业造成严重经济损失。在这里,我们发现具有杀蚜虫活性的吡啶并[1,2-α]嘧啶酮类杂环化合物对 PVY 具有良好的抑制作用。其中,化合物 对 PVY 的抑制活性最好(EC = 104 μg/mL),甚至优于宁南霉素(125 μg/mL)。荧光和 qPCR 结果证实,化合物 可以抑制 中 PVY 的增殖。作用机制的初步实验表明,化合物 与在蚜虫-PVY 相互作用中起关键作用的外壳蛋白(CP)具有良好的结合亲和力。分子对接显示,化合物 可以结合由 Ser52、Glu204 和 Arg208 形成的 CP 口袋。与 CP(5.80 μM)相比,化合物 与 CP(219 μM)、CP(231 μM)和 CP(189 μM)的结合亲和力()值显著降低。萤光素酶测定证实,突变 Ser52、Glu204 和 Arg208 显著影响 CP 的表达水平,从而进一步降低病毒增殖。因此,化合物 的广谱活性为防治 PVY 提供了独特的策略。

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