{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:38:43Z","timestamp":1788950323211,"version":"build-2803163510"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T00:00:00Z","timestamp":1675900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:p><jats:italic>Naegleria fowleri<\/jats:italic> (<jats:italic>N. fowleri<\/jats:italic>) 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). <jats:italic>N. fowleri<\/jats:italic> has been reported globally since its discovery in 1961. Recently a new strain of <jats:italic>N. fowleri<\/jats:italic> 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 <jats:italic>N. fowleri<\/jats:italic> worldwide. Six of these genes encode well-known proteins. In this study, we performed <jats:italic>in-silico<\/jats:italic> 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 <jats:italic>in-vitro<\/jats:italic> studies could validate the findings of our <jats:italic>in-silico<\/jats:italic> analysis and identify potential therapeutic drugs against <jats:italic>N. fowleri<\/jats:italic> infections.<\/jats:p>","DOI":"10.3389\/fmolb.2023.1098217","type":"journal-article","created":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T12:06:25Z","timestamp":1675944385000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["In-silico drug design for the novel Karachi-NF001 strain of brain-eating amoeba: Naegleria fowleri"],"prefix":"10.3389","volume":"10","author":[{"given":"Tayyab","family":"Saleem","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed Babar","family":"Jamal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Badr","family":"Alzahrani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amina","family":"Basheer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumra","family":"Wajid Abbasi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahwish","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashfaq Ur","family":"Rehman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Faheem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/S1473-3099(19)30675-9","article-title":"Naegleria fowleri in Pakistan","volume":"20","author":"Ali","year":"2020","journal-title":"Lancet Infect. 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