Scholarlink

<p>The emergence of multidrug-resistant <i>Neisseria gonorrhoeae</i> has intensified the need for innovative therapeutic strategies. One promising but underexplored target is the Hfq protein, a key regulator in bacterial stress response and pathogenesis. In this study, we employed a computer-aided drug discovery approach to screen phytochemicals from traditionally used anti-gonorrheal plants for their potential to inhibit Hfq. Molecular docking identified several compounds, including Hellebrigenin 3-acetate, Carpaine, β-amyrin, α-amyrin, Rosarin, Oleanolic acid, and Epigallocatechin 3-O-gallate, with binding affinities surpassing that of the reference drug, Ceftriaxone. Molecular dynamics simulations revealed that Carpaine and Oleanolic acid formed the most stable Hfq complexes, exhibiting low RMSD values (0.73&#xa0;nm and 0.66&#xa0;nm) and compact Rg profiles (~ 1.4&#xa0;nm), indicating strong structural stabilization. ADMET analysis suggested moderate intestinal absorption and oral bioavailability, though some compounds showed risks of liver toxicity and CYP2D6 inhibition. Carpaine demonstrated the most favorable binding free energy and prolonged systemic retention, making it an up-and-coming lead candidate. Importantly, evolutionary analysis confirmed the conservation of the Hfq active site, further supporting its viability as a therapeutic target. These findings reveal the potential of plant-derived compounds, particularly Carpaine and Oleanolic acid, as novel Hfq inhibitors, providing a strong foundation for future experimental validation and the development of alternative therapies against multidrug-resistant <i>N. gonorrhoeae</i>.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Computer-aided identification of Neisseria gonorrhoeae’s Bacteriophage-Q-beta inhibitors from selected anti-gonorrheal plants

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月27日

查看全文
  • Badmus Jamiu Damilare,
  • Che Muhammad Khairul-Hisyam Ismail,
  • Blessing O. Awoyemi,
  • Abdullahi Tunde Aborode,
  • Ibukun Faith Michael,
  • Haruna Isiyaku Umar,
  • Omoboyede Victor,
  • Zainab Naeem Abdulsalam,
  • Oluwabusayo Olufunke Awoyomi,
  • Sodiq Fakorede,
  • Ousainou Gomez,
  • Adekunle Adeoye,
  • Olasehinde Omolayo,
  • Isreal Ayobami Onifade,
  • Abdullahi Temitope Jamiu

摘要

The emergence of multidrug-resistant Neisseria gonorrhoeae has intensified the need for innovative therapeutic strategies. One promising but underexplored target is the Hfq protein, a key regulator in bacterial stress response and pathogenesis. In this study, we employed a computer-aided drug discovery approach to screen phytochemicals from traditionally used anti-gonorrheal plants for their potential to inhibit Hfq. Molecular docking identified several compounds, including Hellebrigenin 3-acetate, Carpaine, β-amyrin, α-amyrin, Rosarin, Oleanolic acid, and Epigallocatechin 3-O-gallate, with binding affinities surpassing that of the reference drug, Ceftriaxone. Molecular dynamics simulations revealed that Carpaine and Oleanolic acid formed the most stable Hfq complexes, exhibiting low RMSD values (0.73 nm and 0.66 nm) and compact Rg profiles (~ 1.4 nm), indicating strong structural stabilization. ADMET analysis suggested moderate intestinal absorption and oral bioavailability, though some compounds showed risks of liver toxicity and CYP2D6 inhibition. Carpaine demonstrated the most favorable binding free energy and prolonged systemic retention, making it an up-and-coming lead candidate. Importantly, evolutionary analysis confirmed the conservation of the Hfq active site, further supporting its viability as a therapeutic target. These findings reveal the potential of plant-derived compounds, particularly Carpaine and Oleanolic acid, as novel Hfq inhibitors, providing a strong foundation for future experimental validation and the development of alternative therapies against multidrug-resistant N. gonorrhoeae.