{"paper_id":"5bc333a5-b2de-48d0-b6d2-49ef069ca376","body_text":"Three novel epigenetic-modifying compounds identified as HIV latency-reversing agents in Ghana | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Three novel epigenetic-modifying compounds identified as HIV latency-reversing agents in Ghana Christopher Zaab-Yen Abana, Anthony Twumasi Boateng, Araba Abaidoo-Myles, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7483295/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Human Immunodeficiency Virus (HIV) persists despite antiretroviral therapy (ART) due to latent viral reservoirs that remain undetected by the immune system. A promising cure approach involves using latency-reversing agents (LRAs) to reactivate latent proviruses, enabling immune-mediated clearance. Because HIV latency is regulated by epigenetic modifications of chromatin surrounding the integrated virus, we hypothesized that epigenetic-modifying compounds could function as effective LRAs. We screened 150 such compounds using the J.LAT 10.6 cell line, which harbors a single integrated HIV-GFP reporter. Reactivation was assessed by GFP expression via flow cytometry. Positive hits were screened across multiple J.LAT clones and a primary CD4⁺ T cell latency model, with lead candidates evaluated ex vivo in CD4⁺ T cells isolated from four ART-suppressed individuals (viral load <50 copies/mL). HIV-1 mRNA levels were quantified by RT-qPCR. Screening identified 15 positive hits, of which five (MC1568, Abexinostat, Pracinostat, EPZ2015666, and CXC6258-HCL) induced 20–91% GFP-positive cells. MC1568 showed consistent activity across J.LAT clones (47–91% GFP⁺). In the primary T cell model, three compounds (MC1568, Abexinostat, and Pracinostat) were validated as lead LRAs. Ex vivo, these compounds significantly increased intracellular HIV-1 mRNA expression (6–19-fold) in CD4⁺ T cells from all four participants. We identified three promising LRAs (MC1568, Abexinostat, and Pracinostat) that robustly reactivated latent HIV both in vitro and ex vivo. These findings warrant preclinical evaluation in animal models as potential components of HIV cure strategies. Notably, this is the first study in Ghana to establish a medium- to high-throughput HIV latency reversal screening platform. Epigenetics latency-reversing agents latency HIV Full Text Supplementary Files SupplementaryData1CMLS.pdf Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-7483295\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":528743982,\"identity\":\"4ac6b0a7-40c4-45c9-9d7b-467bb4f3b221\",\"order_by\":0,\"name\":\"Christopher Zaab-Yen Abana\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAklEQVRIiWNgGAWjYFACHhBhA2YyMxhAxCSAOIGAljTStRyGamEgQgt/+9mDnwtqzufx868x/FxQwJA434H54G0ehto8XFokzuQlS884drtYcsYbY+kZBgyJGw+wJVvzMBwvxqXFgCHHQJqH7XbihhtnzJh5QFoaeMykeRiOJTbg0sL/xvg3z79zyFr4v+HXIpFjJs3bdiBxw/keiJb5DDxsQC01OLVI3HiXZs3bl5w4cwZbsTSPgYTxBmY2Y8s5BgdwauHvzz18m+ebXWI//+GNn3n+2MjOb29+eONNRR1OLUj2JYBJBgNwHEFIAoD/AISWh5heR4SWUTAKRsEoGCEAAN5JU0wia1JTAAAAAElFTkSuQmCC\",\"orcid\":\"https://orcid.org/0000-0002-9387-6778\",\"institution\":\"Virology Department, Noguchi Memorial Institute for Medical Research, University of Ghana\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Christopher\",\"middleName\":\"Zaab-Yen\",\"lastName\":\"Abana\",\"suffix\":\"\"},{\"id\":528743983,\"identity\":\"22e6371f-6d98-42cc-948b-2ecba8366966\",\"order_by\":1,\"name\":\"Anthony Twumasi Boateng\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Virology Department, Noguchi Memorial Institute for Medical Research, University of Ghana\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Anthony\",\"middleName\":\"Twumasi\",\"lastName\":\"Boateng\",\"suffix\":\"\"},{\"id\":528743984,\"identity\":\"ac003f1d-cad9-48a8-9d37-0b496ea5d7d3\",\"order_by\":2,\"name\":\"Araba Abaidoo-Myles\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Virology Department, Noguchi Memorial Institute for Medical Research, University of Ghana\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Araba\",\"middleName\":\"\",\"lastName\":\"Abaidoo-Myles\",\"suffix\":\"\"},{\"id\":528743985,\"identity\":\"e63d9590-964f-42da-ba22-259d02c48167\",\"order_by\":3,\"name\":\"Prince Adom Nartey\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Virology Department, Noguchi Memorial Institute for Medical Research, University of Ghana\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Prince\",\"middleName\":\"Adom\",\"lastName\":\"Nartey\",\"suffix\":\"\"},{\"id\":528743986,\"identity\":\"7f49c58b-7e90-47a1-86ae-306e4208ec6c\",\"order_by\":4,\"name\":\"Charlotte Borteley Bortey\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Virology Department, Noguchi Memorial Institute for Medical Research, University of Ghana\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Charlotte\",\"middleName\":\"Borteley\",\"lastName\":\"Bortey\",\"suffix\":\"\"},{\"id\":528743987,\"identity\":\"88672079-f625-4908-b7bc-e270af41f076\",\"order_by\":5,\"name\":\"Darius N. 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A promising cure approach involves using latency-reversing agents (LRAs) to reactivate latent proviruses, enabling immune-mediated clearance. Because HIV latency is regulated by epigenetic modifications of chromatin surrounding the integrated virus, we hypothesized that epigenetic-modifying compounds could function as effective LRAs.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eWe screened 150 such compounds using the J.LAT 10.6 cell line, which harbors a single integrated HIV-GFP reporter. Reactivation was assessed by GFP expression via flow cytometry. Positive hits were screened across multiple J.LAT clones and a primary CD4⁺ T cell latency model, with lead candidates evaluated ex vivo in CD4⁺ T cells isolated from four ART-suppressed individuals (viral load \\u0026lt;50 copies/mL). HIV-1 mRNA levels were quantified by RT-qPCR.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eScreening identified 15 positive hits, of which five (MC1568, Abexinostat, Pracinostat, EPZ2015666, and CXC6258-HCL) induced 20–91% GFP-positive cells. MC1568 showed consistent activity across J.LAT clones (47–91% GFP⁺). In the primary T cell model, three compounds (MC1568, Abexinostat, and Pracinostat) were validated as lead LRAs. Ex vivo, these compounds significantly increased intracellular HIV-1 mRNA expression (6–19-fold) in CD4⁺ T cells from all four participants.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eWe identified three promising LRAs (MC1568, Abexinostat, and Pracinostat) that robustly reactivated latent HIV both in vitro and ex vivo. These findings warrant preclinical evaluation in animal models as potential components of HIV cure strategies. 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