In-silico drug design for the novel Karachi-NF001 strain of brain-eating amoeba: Naegleria fowleri

Tayyab Saleem; Syed Babar Jamal; Badr Alzahrani; Amina Basheer; Sumra Wajid Abbasi; Mahwish Ali; Ashfaq Ur Rehman; Muhammad Faheem

doi:10.3389/fmolb.2023.1098217

In-silico drug design for the novel Karachi-NF001 strain of brain-eating amoeba: Naegleria fowleri

Front Mol Biosci. 2023 Feb 9:10:1098217. doi: 10.3389/fmolb.2023.1098217. eCollection 2023.

Authors

Tayyab Saleem¹, Syed Babar Jamal², Badr Alzahrani³, Amina Basheer², Sumra Wajid Abbasi², Mahwish Ali², Ashfaq Ur Rehman⁴, Muhammad Faheem²

Affiliations

¹ Department of Life Technologies, Faculty of Technology, University of Turku, Turku, Finland.
² Department of Biological Sciences, National University of Medical Sciences, Rawalpindi, Pakistan.
³ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, Saudi Arabia.
⁴ Department of Biochemistry and Molecular Biology, University of California, Irvine, Irvine, CA, United States.

Abstract

Naegleria fowleri (N. fowleri) is a free-living thermophilic amoeba of fresh water and soil. The amoeba primarily feeds on bacteria but can be transmitted to humans upon contact with freshwater sources. Furthermore, this brain-eating amoeba enters the human body through the nose and travels to the brain to cause primary amebic meningoencephalitis (PAM). N. fowleri has been reported globally since its discovery in 1961. Recently a new strain of N. fowleri named Karachi-NF001 was found in a patient who had traveled from Riyadh, Saudi Arabia to Karachi in 2019. There were 15 unique genes identified in the genome of the Karachi-NF001 strain compared to all the previously reported strains of N. fowleri worldwide. Six of these genes encode well-known proteins. In this study, we performed in-silico analysis on 5 of these 6 proteins, namely, Rab family small GTPase, NADH dehydrogenase subunit 11, two Glutamine-rich protein 2 proteins (locus tags: 12086 and 12110), and Tigger transposable element-derived protein 1. We conducted homology modeling of these 5 proteins followed by their active site identification. These proteins were subjected to molecular docking against 105 anti-bacterial ligand compounds as potential drugs. Subsequently, the 10 best-docked compounds were determined for each protein and ranked according to the number of interactions and their binding energies. The highest binding energy was recorded for the two Glutamine-rich protein 2 proteins with different locus tags, and results have shown that the protein-inhibitor complex was stable throughout the simulation run. Moreover, future in-vitro studies could validate the findings of our in-silico analysis and identify potential therapeutic drugs against N. fowleri infections.

Keywords: Karachi; Naegleria fowleri; Pakistan; brain-eating amoeba; in-silico; molecular docking; pathogenic proteins.