2. Academic Validation
  3. Discovery of Novel Inhibitors Targeting Fungal Chitin Deacetylase via Virtual Screening for Plant Disease Control

Discovery of Novel Inhibitors Targeting Fungal Chitin Deacetylase via Virtual Screening for Plant Disease Control

  • J Agric Food Chem. 2025 Apr 16;73(15):8886-8896. doi: 10.1021/acs.jafc.5c00847.
Huan Xu 1,  Yingchen Li 2,  Xiaoyan Cao 1,  Qi He 1,  Binyan Jin 1,  Lingjie Dai 1,  Xinyuan Zhang 1,  Xiaoming Zhang 1,  Qiang Bian 3,  Qing Yang 2,  Li Zhang 1
Affiliations

Affiliations

  • 1 Innovation Center of Pesticide Research, Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, China.
  • 2 State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection and Shenzhen Agricultural Genome Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
  • 3 National Pesticide Engineering Research Center (Tianjin), College of Chemistry, Nankai University, Tianjin 300071, China.
PMID: 40173383 DOI: 10.1021/acs.jafc.5c00847
Abstract

Fungal chitin deacetylase (CDA) plays a crucial role in pathogen-plant interactions, which is regarded as an innovative and promising target for fungicides. In this study, a pharmacophore-based virtual screening strategy was employed to identify compounds VS-24 and VS-25 as potent inhibitors against Puccinia striiformis f. sp. tritici CDA (PstCDA). Further bioassays demonstrated that VS-24 exhibited a protective effect of 61.2% against rice blast at 100 μg/mL, while VS-25 showed a superior protective effect of 45.5% against corn rust at 5 μg/mL, both superior to the reported CDA inhibitor benzohydroxamic acid (BHA). Molecular dynamics simulations revealed that multiple key interactions involving the Zn2+ ion and residues His207 and Tyr152 of PstCDA are critical for the binding of VS-24 or VS-25, with electrostatic interactions contributing most significantly to the binding free energy. Finally, toxicity predictions confirmed the potential biosafety of VS-24 and VS-25. Overall, this study identified two promising lead compounds targeting Fungal CDA to control plant diseases.

Keywords

chitin deacetylase; pharmacophore; plant fungal disease control; virtual screening.

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