In Silico Repurposing of Fluoxetine: Targeting the MvfR Protein of Pseudomonas aeruginosa
Abstract
Fluoxetine is mainly used as a selective serotonin reuptake inhibitor. However, studies have shown that it may also have antimicrobial properties and antivirulence effects. This study utilized an in-silico repurposing and drug repositioning methodology on fluoxetine (an antidepressant drug) against Pseudomonas aeruginosa infection. The goal was to focus on a protein called MvfR/PqsR. This MvfR/PqsR protein is important, for controlling how bad a germ is and how it forms a group of germs that stick together. To find some compounds that can work with this MvfR/PqsR protein we used computers to test a lot of different things. We also used computers to see how a medicine called fluoxetine interacts with the MvfR/PqsR protein. Then we made some versions of fluoxetine that are similar but a little different to see if they can work better with the MvfR/PqsR protein. These derivatives were then checked using docking analysis and ADMET profiling. The assessment included how well they bind, their pharmacokinetics and safety details. Lab experiments were also done to confirm the results. These tests looked at the activity and biofilm inhibition of fluoxetine against Mvfr protein. Fluoxetine showed a binding affinity with the MvfR receptor at -8.4 kcal/mol. The antibacterial activity was confirmed through experiments. The minimum amount needed to inhibit growth was 0.5 mg/mL. A significant decrease in biofilm biomass was seen at p = 0.005. This shows a reduction in biofilm. Some…
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