Elucidating novel antibacterial compounds from the NPASS database against the FimH lectin domain for the treatment of urinary tract infections: an in-silico study

Abstract

The increase in multidrug-resistant pathogens in urinary tract infections (UTIs) among communities and hospitals threatens our ability to treat these common pathogens. Uropathogenic Escherichia coli (UPEC) strains are the most frequent uropathies linked to the development of UTIs. This work aims to introduce bioactive natural products via virtual screening of small molecules from a public database to prevent biofilm formation by inhibiting FimH, a type 1 fimbriae that plays a crucial role in UPEC pathogenicity. A total of 30926 small molecules from the NPASS database were subjected to screening via molecular docking. Followed by performing in silico ADME studies, seven molecules showed promising docking results ranging from −6.8 to −8.7 kcal/mol. As a result of the docking score findings, 100 ns Molecular dynamics (MD) simulations were performed. Based on MM-PBSA analysis, NPC313334 ligand showed high binding affinity −42 and stability with the binding pocket of FimH protein during molecular dynamic simulations. DFT calculations were also performed on the ligands to calculate the HOMO-LUMO energies of the compounds in order to an idea about their structure and reactivity. This research suggests that NPC313334 may be a possible antibacterial drug candidate that targets FimH to reduce the number of UPEC-related urinary tract infections.

Communicated by Ramaswamy H. Sarma

Keywords:

• Antibiofilm
• urinary tract infections
• molecular docking
• molecular dynamics
• FimH
• type 1 fimbriae

Disclosure statement

All the authors declare no conflict of interest.

Funding

This work did not have any fund.

Authors contribution

Mrtatha Al-Zrkani contributes by methodology, data curation, analyzing results as the corresponding author. Ahmad Al-Khdhairawi wrote the original draft manuscript. Amaal Mohammed Salih Nasr provided critical feedback. Dhurgham Al-Fahad and Marwah Al Shouber equally contribute to shaping the experimental framework. Rafid A. Abdulkareem project administration and overall direction and planning.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.