{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T12:39:32Z","timestamp":1793104772664,"version":"4.5.0"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T00:00:00Z","timestamp":1717977600000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The naturally occurring dipeptide Tryptophylglycine (WG) is enhanced in human immunodeficiency virus (HIV-1) infected Elite Controllers (EC). We have shown that this dipeptide has an anti-HIV-1 effect and evaluated now its synergistic antiretroviral activity, in combination with current antiretrovirals against multi-drug resistant HIV-1 isolates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Drug selectivity assay with WG-am and ARVs agains HIV-1 resistant isolates were carried out. Subsequently, two methods, Chou-Talalay\u2019s Combination Index (CI) and ZIP synergy score (SS), were used to quantify the synergism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>WG-am had a moderate\/strong synergism with the four tested antiretrovirals: raltegravir, tenofovir, efavirenz, darunavir. WG-am:TDF had strong synergism at ED50, ED75, ED90 (CI: &amp;lt;0.2) in isolates resistant to protease inhibitors or integrase strand inhibitors (INSTI), and a slightly less synergism in isolates resistant to non-nucleoside or nucleotide reverse transcriptase inhibitors. WG-am combined with each of the four drugs inhibited all drug-resistant isolates with over 95% reduction at maximum concentration tested. The highest selectivity indexes (CC50\/ED50) were in INSTI-resistant isolates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data suggest that WG, identified as occurring and enhanced in Elite Controllers has a potential to become a future treatment option in patients with HIV-1 strains resistant to any of the four major categories of anti-HIV-1 compounds.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2024.1334126","type":"journal-article","created":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T20:24:15Z","timestamp":1718223855000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Broad synergistic antiviral efficacy between a novel elite controller-derived dipeptide and antiretrovirals against drug-resistant HIV-1"],"prefix":"10.3389","volume":"14","author":[{"given":"Federica","family":"Giammarino","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"S\u00f6nnerborg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Ce\u00f1a-Diez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,6,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1097\/QAD.0000000000002740","article-title":"High-throughput sequencing reveals a high prevalence of pretreatment HIV-1 drug resistance in Sweden","volume":"35","author":"Andersson","year":"2021","journal-title":"AIDS"},{"key":"B2","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1097\/QAI.0000000000003027","article-title":"High levels of pretreatment HIV-1 drug resistance mutations among South African women who acquired HIV during a prospective study","volume":"91","author":"Beesham","year":"2022","journal-title":"J. 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