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<p>The global rise of multidrug-resistant&#xa0;<i>Neisseria gonorrhoeae</i>&#xa0;underscores the urgent need for innovative therapeutics. This study targets Obg GTPase, a conserved bacterial enzyme critical for ribosome biogenesis and stress response, using an in-silico approach to identify plant-derived inhibitors. A library of 157 phytochemicals from 18 anti-gonorrheal medicinal plants was screened using an integrated computational pipeline, including molecular docking, drug-likeness screening, ADMET profiling, and molecular dynamics simulations. Among the screened compounds, arjunic acid, formononetin, and isovestitol emerged as our top candidates as they exhibited strong binding affinities, favorable pharmacokinetic properties, and stable interactions within the Obg GTPase active site. ADMET prediction revealed moderate intestinal absorption (60–74%), low P-glycoprotein inhibition (30–47%), and acceptable toxicity thresholds. Molecular dynamics simulations (150&#xa0;ns) revealed stable protein–ligand complexes, with arjunic acid showing the most favorable binding free energy (− 33.17&#xa0;kcal/mol) compared to ceftriaxone (− 20.04&#xa0;kcal/mol). Structural stability metrics, including RMSD (&lt; 1.15&#xa0;nm) and radius of gyration (~ 3.0&#xa0;nm), validated the conformational integrity of the complexes. These findings highlight Obg GTPase as a viable therapeutic target and support the potential of plant-derived compounds, particularly arjunic acid, formononetin, and isovestitol, as novel anti-gonorrheal agents. This study bridges ethnopharmacology and computational drug discovery, laying the pedestal for future experimental validation and the development of alternative treatments against drug-resistant <i>N. gonorrhoeae</i> and other bacterial pathogens.</p> Graphical Abstract <p></p>

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In silico identification of GTPase inhibitors from selected anti-gonorrheal plants against Neisseria gonorrhoeae

  • 期刊论文

  • 发表日期：

    2025年10月30日

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  • Blessing O. Awoyemi,
  • Badmus Jamiu Damilare,
  • Abdullahi Tunde Aborode,
  • Che Muhammad Khairul Hisyam Ismail,
  • Abdulqohar Adebayo,
  • Haruna Isiyaku Umar,
  • Ibrahim Akindeji Makinde,
  • Ridwan Opeyemi Bello,
  • Sodiq Fakorede,
  • Mohammed M. Alshehri,
  • Ahmed F. Alanazi

摘要

The global rise of multidrug-resistant Neisseria gonorrhoeae underscores the urgent need for innovative therapeutics. This study targets Obg GTPase, a conserved bacterial enzyme critical for ribosome biogenesis and stress response, using an in-silico approach to identify plant-derived inhibitors. A library of 157 phytochemicals from 18 anti-gonorrheal medicinal plants was screened using an integrated computational pipeline, including molecular docking, drug-likeness screening, ADMET profiling, and molecular dynamics simulations. Among the screened compounds, arjunic acid, formononetin, and isovestitol emerged as our top candidates as they exhibited strong binding affinities, favorable pharmacokinetic properties, and stable interactions within the Obg GTPase active site. ADMET prediction revealed moderate intestinal absorption (60–74%), low P-glycoprotein inhibition (30–47%), and acceptable toxicity thresholds. Molecular dynamics simulations (150 ns) revealed stable protein–ligand complexes, with arjunic acid showing the most favorable binding free energy (− 33.17 kcal/mol) compared to ceftriaxone (− 20.04 kcal/mol). Structural stability metrics, including RMSD (< 1.15 nm) and radius of gyration (~ 3.0 nm), validated the conformational integrity of the complexes. These findings highlight Obg GTPase as a viable therapeutic target and support the potential of plant-derived compounds, particularly arjunic acid, formononetin, and isovestitol, as novel anti-gonorrheal agents. This study bridges ethnopharmacology and computational drug discovery, laying the pedestal for future experimental validation and the development of alternative treatments against drug-resistant N. gonorrhoeae and other bacterial pathogens.

Graphical Abstract