A1 Refereed original research article in a scientific journal
In-silico drug design for the novel Karachi-NF001 strain of brain-eating amoeba:Naegleria fowleri
Authors: Saleem Tayyab, Jamal Syed Babar Jamal, Alzahrani Badr, Basheer Amina, Abbasi Sumra Wajid, Ali Mahwish, Rehman Ashfaq Ur, Faheem Muhammad
Publisher: FRONTIERS MEDIA SA
Publishing place: LAUSANNE
Publication year: 2023
Journal: Frontiers in Molecular Biosciences
Journal name in source: FRONTIERS IN MOLECULAR BIOSCIENCES
Journal acronym: FRONT MOL BIOSCI
Article number: 1098217
Volume: 10
Number of pages: 9
eISSN: 2296-889X
DOI: https://doi.org/10.3389/fmolb.2023.1098217
Web address : https://doi.org/10.3389/fmolb.2023.1098217
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/386802606
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.
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