Drug Repurposing Identifies Natamycin and Avacopan as Urease-Targeted Therapeutic Candidates Against Helicobacter...

Area of Science:

• Microbiology
• Pharmacology
• Computational Chemistry

Background:

• Antimicrobial resistance necessitates novel treatments for persistent infections like Helicobacter pylori.
• H. pylori urease is a critical virulence factor enabling survival in the gastric environment.

Purpose of the Study:

• To identify potential inhibitors of H. pylori urease from FDA-approved drugs.
• To evaluate the efficacy of identified inhibitors against H. pylori in vitro.

Main Methods:

• Virtual screening of 1773 FDA-approved drugs against H. pylori urease.
• Molecular dynamics simulations to assess drug-enzyme complex stability and binding.
• In vitro validation of selected drug candidates (Avacopan, Natamycin) for urease inhibition and antibacterial activity.

Main Results:

• Avacopan and Natamycin demonstrated significant binding affinity to H. pylori urease.
• Both compounds effectively inhibited urease activity and exhibited antibacterial effects against clinical H. pylori isolates.
• Natamycin showed stronger overall inhibition, while Avacopan displayed higher stability in simulations.

Conclusions:

• Avacopan and Natamycin are promising candidates for drug repurposing against H. pylori infections.
• Targeting H. pylori urease offers a viable strategy to combat antimicrobial resistance.
• Further research is needed to elucidate specific mechanisms and optimize therapeutic application.