{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T14:41:26Z","timestamp":1767969686367,"version":"3.49.0"},"reference-count":69,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"MOHW | Korea National Institute of Health","award":["2022-NI-006"],"award-info":[{"award-number":["2022-NI-006"]}]},{"name":"MOHW | Korea National Institute of Health","award":["2020-ER-5106"],"award-info":[{"award-number":["2020-ER-5106"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2024,10,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Human immunodeficiency virus-1 (HIV-1) encodes a transcriptional factor called Tat, which is critical for viral transcription. Tat-mediated transcription is highly ordered apart from the cellular manner; therefore, it is considered a target for developing anti-HIV-1 drugs. However, drugs targeting Tat-mediated viral transcription are not yet available. Our high-throughput screen of a compound library employing a dual-reporter assay identified a 1,3,4-oxadiazole scaffold against Tat and HIV-1 infection. Furthermore, a serial structure\u2013activity relation (SAR) study performed with biological assays found 1,3,4-oxadiazole derivatives (\n              <jats:bold>9<\/jats:bold>\n              and\n              <jats:bold>13<\/jats:bold>\n              ) containing indole and acetamide that exhibited potent inhibitory effects on HIV-1 infectivity, with half-maximal effective concentrations (EC\n              <jats:sub>50<\/jats:sub>\n              ) of 0.17 (\n              <jats:bold>9<\/jats:bold>\n              ) and 0.24 \u00b5M (\n              <jats:bold>13<\/jats:bold>\n              ), respectively. The prominent derivatives specifically interfered with the viral transcriptional step without targeting other infection step(s) and efficiently inhibited the HIV-1 replication cycle in the T cell lines and peripheral blood mononuclear cells infected with HIV-1. Additionally, compared to the wild type, the compounds exhibited similar potency against anti-retroviral drug-resistant HIV-1 strains. In a series of mode-of-action studies, the compounds inhibited the ejection of histone H3 for facilitating viral transcription on the long-terminal repeat (LTR) promoter. Furthermore, SAHA (a histone deacetylase inhibitor) treatment abolished the compound potency, revealing that the compounds can possibly target Tat-regulated epigenetic modulation of LTR to inhibit viral transcription. Overall, our screening identified novel 1,3,4-oxadiazole compounds that inhibited HIV-1 Tat, and subsequent SAR-based optimization led to the derivatives\n              <jats:bold>9<\/jats:bold>\n              and\n              <jats:bold>13<\/jats:bold>\n              development that could be a promising scaffold for developing a new class of therapeutic agents for HIV-1 infection.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.00643-24","type":"journal-article","created":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T13:02:11Z","timestamp":1725454931000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Discovery of new acetamide derivatives of 5-indole-1,3,4-oxadiazol-2-thiol as inhibitors of HIV-1 Tat-mediated viral transcription"],"prefix":"10.1128","volume":"68","author":[{"given":"YoungHyun","family":"Shin","sequence":"first","affiliation":[{"name":"Division of Chronic Viral Diseases, Center for Emerging Virus Research, Korea National Institute of Health, Cheongju, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chul Min","family":"Park","sequence":"additional","affiliation":[{"name":"Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea"},{"name":"Medicinal Chemistry and Pharmacology, Korea University of Science and Technology, Daejeon, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong-Eun","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Chronic Viral Diseases, Center for Emerging Virus Research, Korea National Institute of Health, Cheongju, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sungmin","family":"Kim","sequence":"additional","affiliation":[{"name":"Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang-Yeop","family":"Lee","sequence":"additional","affiliation":[{"name":"Research Center for Bioconvergence Analysis, Ochang Center, Korea Basic Science Institute, Cheongju-si, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Won-Hui","family":"Jeon","sequence":"additional","affiliation":[{"name":"Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong Gi","family":"Kim","sequence":"additional","affiliation":[{"name":"Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea"},{"name":"Medicinal Chemistry and Pharmacology, Korea University of Science and Technology, Daejeon, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Songmee","family":"Bae","sequence":"additional","affiliation":[{"name":"Division of Chronic Viral Diseases, Center for Emerging Virus Research, Korea National Institute of Health, Cheongju, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7999-5554","authenticated-orcid":true,"given":"Cheol-Hee","family":"Yoon","sequence":"additional","affiliation":[{"name":"Division of Chronic Viral Diseases, Center for Emerging Virus Research, Korea National Institute of Health, Cheongju, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2015.35"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00580"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2021.10.004"},{"key":"e_1_3_4_5_2","first-page":"14","article-title":"Chronic hepatitis B and HIV coinfection","volume":"31","author":"Corcorran MA","year":"2023","unstructured":"Corcorran MA, Kim N. 2023. 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