Structural-based Study to Identify the Repurposed Candidates against Bacterial Infections

Area of Science:

• Computational drug discovery
• Antimicrobial resistance research
• Pharmacology and medicinal chemistry

Background:

• Bacterial infections caused by Gram-positive and Gram-negative bacteria pose a significant global health challenge.
• There is a critical need for novel therapeutic strategies and the exploration of existing drugs for repurposing against bacterial pathogens.

Purpose of the Study:

• To computationally screen recently US-FDA-approved drugs (2019-2023) for potential repurposing against bacterial targets.
• To identify promising drug candidates with favorable binding conformations and stable interactions with key bacterial enzymes.

Main Methods:

• Literature-based identification of bacterial targets (Gram-positive and Gram-negative).
• Selection of ligands from FDA-approved drug lists (last 5 years).
• Molecular docking and molecular dynamics simulations using Schrödinger software (LigPrep, Protein Preparation Wizard, GlideDock, Desmond).

Main Results:

• Out of 202 FDA-approved drugs, 77 were selected for docking; 21 showed energetically favorable binding.
• Molecular dynamics simulations revealed stable conformations for triclabendazole with Gram-negative bacteria's topoisomerase II.
• Solriamfetol demonstrated stable dynamic conformation with Gram-positive bacteria's restriction endonuclease.

Conclusions:

• The study identified potential drug repurposing candidates for Gram-positive and Gram-negative bacterial infections.
• Triclabendazole and solriamfetol are highlighted for their promising interactions, warranting further experimental validation.