{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T17:50:20Z","timestamp":1779299420587,"version":"3.51.4"},"reference-count":43,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T00:00:00Z","timestamp":1662336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bowie State University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The pathogenic form of thermophilic Naegleria sp. i.e., Naegleria fowleri, also known as brain eating amoeba, causes primary amoebic encephalitis (PAM) with a &gt;97% fatality rate. To date, there are no specific drugs identified to treat this disease specifically. The present antimicrobial combinatorial chemotherapy is hard on many patients, especially children. Interestingly, Naegleria fowleri has complex lipid biosynthesis pathways like other protists and also has a strong preference to utilize absorbed host lipids for generating energy. The ergosterol biosynthesis pathway provides a unique drug target opportunity, as some of the key enzymes involved in this pathway are absent in humans. Sterol 24-C Methyltransferase (SMT) is one such enzyme that is not found in humans. To select novel inhibitors for this enzyme, alkaloids and terpenoids inhibitors were screened and tested against two isozymes of SMT identified in N. gruberi (non-pathogenic) as well as its homolog found in yeast, i.e., ERG6. Five natural product derived inhibitors i.e., Cyclopamine, Chelerythrine, Berberine, Tanshinone 2A, and Catharanthine have been identified as potential drug candidates based on multiple criteria including binding affinity, ADME scores, absorption, and, most importantly, its ability to cross the blood brain barrier. This study provides multiple leads for future drug exploration against Naegleria fowleri.<\/jats:p>","DOI":"10.3390\/molecules27175727","type":"journal-article","created":{"date-parts":[[2022,9,7]],"date-time":"2022-09-07T01:51:57Z","timestamp":1662515517000},"page":"5727","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Virtual Screening of Alkaloid and Terpenoid Inhibitors of SMT Expressed in Naegleria sp."],"prefix":"10.3390","volume":"27","author":[{"given":"Jason","family":"Abraham","sequence":"first","affiliation":[{"name":"Department of Natural Sciences, Bowie State University, 14000 Jericho Park Rd., Bowie, MD 20715, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neha","family":"Chauhan","sequence":"additional","affiliation":[{"name":"Department of Chemistry & Biochemistry, University of Texas El Paso, 500 W. University Ave., El Paso, TX 79968, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Supriyo","family":"Ray","sequence":"additional","affiliation":[{"name":"Department of Natural Sciences, Bowie State University, 14000 Jericho Park Rd., Bowie, MD 20715, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1016\/j.pt.2019.06.011","article-title":"Naegleria fowleri","volume":"35","year":"2019","journal-title":"Trends Parasitol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1093\/cid\/cis309","article-title":"Is ritual cleansing a missing link between fatal infection and brain-eating amoebae?","volume":"54","author":"Siddiqui","year":"2012","journal-title":"Clin. Infect. 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