Liu Yuansheng, Liu Jinfeng, Xia Yeqiang, Chen Wei, Li Yingchen, He Xiao, Yang Qing
School of Bioengineering, Dalian University of Technology, Dalian, China.
State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing, China.
Pest Manag Sci. 2025 Feb;81(2):777-785. doi: 10.1002/ps.8480. Epub 2024 Oct 15.
Chitin synthase (CHS) is an important target for pesticide development as chitin biosynthesis is essential for the survival and reproduction of various organisms, such as oomycetes, fungi and insects. Small-molecule inhibitors of CHS have potential applications for the control of agricultural pests and diseases.
In this study, exploiting the cryo-EM structures of PsChs1, the CHS indispensable to the sporangial production and virulence of soybean root rot pathogenic oomycete Phytophthora sojae, a virtual screening method combining by molecular docking, inhibitory activity measurement and biological activity determination was conducted, to identify novel small-molecule inhibitors of CHS. A chemical library containing ≈1.8 million compounds was screened, and four potent inhibitors (HS-20, HS-24, HS-36 and HS-40) were identified. Amongst these compounds, HS-20 showed the most potent inhibitory activity with a K value of 4.2 ± 0.2 μM. Besides inhibitory activities towards PsChs1, these compounds were effective in decreasing sporangial production and preventing zoospore infection. When inoculated with zoospores, HS-20 and HS-24 completely inhibited the growth of P. sojae, suggesting their potential in its prevention and control.
This study identified four new compounds with potent chitin synthase (CHS) inhibitory activity, all of which significantly reduce sporangia production and zoospore infection. It also presents promising in silico techniques and small molecule candidates for the design and development of novel CHS inhibitors. © 2024 Society of Chemical Industry.
几丁质合酶（CHS）是农药开发的重要靶点，因为几丁质生物合成对于卵菌、真菌和昆虫等各种生物体的生存和繁殖至关重要。CHS的小分子抑制剂在农业病虫害防治方面具有潜在应用价值。
在本研究中，利用大豆根腐病致病卵菌大豆疫霉孢子囊产生和毒力所必需的CHS即PsChs1的冷冻电镜结构，开展了一种结合分子对接、抑制活性测定和生物活性测定的虚拟筛选方法，以鉴定新型CHS小分子抑制剂。对一个包含约180万种化合物的化学文库进行了筛选，鉴定出四种强效抑制剂（HS-20、HS-24、HS-36和HS-40）。在这些化合物中，HS-20表现出最强的抑制活性，K值为4.2±0.2μM。除了对PsChs1具有抑制活性外，这些化合物还能有效减少孢子囊的产生并防止游动孢子感染。用游动孢子接种时，HS-20和HS-24完全抑制了大豆疫霉的生长，表明它们在防治大豆疫霉方面具有潜力。
本研究鉴定出四种具有强效几丁质合酶（CHS）抑制活性的新化合物，所有这些化合物均能显著减少孢子囊产生和游动孢子感染。该研究还展示了用于新型CHS抑制剂设计和开发的有前景的计算机技术和小分子候选物。© 2024化学工业协会。
