{
  "id": 14094406,
  "title": "Structure-Based Drug Design of Novel Inhibitors Targeting the Thiamine Biosynthesis Pathway in Bacteria",
  "url": "https://urgent.news/2026/10/12/structure-based-drug-design-of-novel-inhibitors-targeting-the",
  "topic": "science",
  "section": "Science",
  "published": "2026-10-12T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.10.05.756923v1?rss=1"
  },
  "original_language": "en",
  "account": "Antibiotic resistance poses a significant problem, as current antibiotics often lack sufficient target selectivity and contribute to the issue of mismanagement. The bacterial thiamine biosynthesis pathway serves as an attractive alternative, as it is vital for bacterial survival yet absent in humans. Disruptions in this pathway have demonstrated reduced mutational tolerance and virulence defects, providing a promising avenue for drug development.\n\nThiamine phosphate synthase, a crucial bottleneck enzyme that connects thiazole and pyrimidine moieties to create thiamine monophosphate, was targeted for inhibitor development. To achieve this, a structure-based drug design pipeline was employed. High-throughput virtual screening of approximately 1.5 million molecules ensured comprehensive exploration of chemical space. This was followed by R-group substitution for lead optimization.\n\nFurther analysis of Structure-Activity Relationships (SAR) upon molecular mutants unveiled patterns among R-group interactions linked to catalytic residues across various scaffolds. Additionally, ADMET screening and validation using molecular dynamics simulations led to the discovery of a potent, orally bioavailable broad-spectrum bactericidal molecule.",
  "summary": "Current generation antibiotics are limited by poor target selectivity and are often mismanaged, leading to widespread antimicrobial resistance. The bacterial thiamine biosynthesis pathway offers compelling alternative since it is highly essential for bacterial survival and yet absent in humans. Genetic perturbations within pathway lead to documented auxotrophy and virulence defects, indicating…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}