State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Huaxi District, Guiyang 550025, China.
State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Huaxi District, Guiyang 550025, China; School of Biological Sciences, Guizhou Education University, Guiyang 550018, China.
Bioorg Chem. 2022 Nov;128:106054. doi: 10.1016/j.bioorg.2022.106054. Epub 2022 Jul 22.
To explore the novel compounds with high antiviral activity, three series ferulic acid derivatives containing amide moiety were gradually designed and synthesized based on antiviral activity tracking. The bioassay results exhibited that some target compounds had notable antiviral activities against tomato spotted wilt virus (TSWV) and cucumber mosaic virus (CMV). Compounds Y1, Y2, Y8, Z1 and Z2 presented splendid curative, protective, and inactivating activities to TSWV and CMV at 500 μg/mL. Especially, these compounds displayed outstanding inactivating effects on TSWV with the EC values of 225.9, 126.1, 224.6, 216.1, and 147.3 μg/mL, which were superior to ningnanmycin (249.1 μg/mL) and ribavirin (315.7 μg/mL). Furthermore, the antiviral mechanisms of compound Y2 were investigated by conducting microscale thermophoresis experiment and molecular docking experiment. The results suggested that compound Y2 performed excellent binding affinity to TSWV coat protein (TSWV CP) with the binding constant of 2.14 μM, which due to two strong hydrogen bonds of compound Y2 to the key amino acids ARG94 of TSWV CP. Therefore, compound Y2 can be regarded as a leading structure for development of the potential antiviral agent.
为了探索具有高抗病毒活性的新型化合物，我们基于抗病毒活性跟踪，逐步设计并合成了三个含有酰胺结构的阿魏酸衍生物系列。生物测定结果表明，一些目标化合物对番茄斑萎病毒（TSWV）和黄瓜花叶病毒（CMV）具有显著的抗病毒活性。在 500μg/mL 时，化合物 Y1、Y2、Y8、Z1 和 Z2 对 TSWV 和 CMV 表现出极好的治疗、保护和灭活活性。特别是，这些化合物对 TSWV 表现出出色的灭活作用，EC 值分别为 225.9、126.1、224.6、216.1 和 147.3μg/mL，优于宁南霉素（249.1μg/mL）和利巴韦林（315.7μg/mL）。此外，通过微量热泳动实验和分子对接实验研究了化合物 Y2 的抗病毒机制。结果表明，化合物 Y2 与 TSWV 外壳蛋白（TSWV CP）具有出色的结合亲和力，结合常数为 2.14μM，这归因于化合物 Y2 与 TSWV CP 的关键氨基酸 ARG94 形成了两个强氢键。因此，化合物 Y2 可以被视为开发潜在抗病毒药物的先导结构。
