{"doi":"10.1016/j.jbc.2024.107701","title":"A heterocyclic compound inhibits viral release by inducing cell surface BST2/Tetherin/CD317/HM1.24","abstract":"The introduction of combined antiretroviral therapy (cART) has greatly improved the quality of life of human immunodeficiency virus type 1 (HIV-1)-infected individuals. Nonetheless, the ever-present desire to seek out a full remedy for HIV-1 infections makes the discovery of novel antiviral medication compelling. Owing to this, a new late-stage inhibitor, Lenacapavir/Sunlenca, an HIV multi-phase suppressor, was clinically authorized in 2022. Besides unveiling cutting-edge antivirals inhibiting late-stage proteins or processes, newer therapeutics targeting host restriction factors hold promise for the curative care of HIV-1 infections. Notwithstanding, bone marrow stromal antigen 2 (BST2)/Tetherin/CD317/HM1.24, which entraps progeny virions is an appealing HIV-1 therapeutic candidate. In this study, a novel drug screening system was established, using the Jurkat/Vpr-HiBiT T cells, to identify drugs that could obstruct HIV-1 release; the candidate compounds were selected from the Ono Pharmaceutical compound library. Jurkat T cells expressing Vpr-HiBiT were infected with NL4-3, and the amount of virus release was quantified indirectly by the amount of Vpr-HiBiT incorporated into the progeny virions. Subsequently, the candidate compounds that suppressed viral release were used to synthesize the heterocyclic compound, HT-7, which reduces HIV-1 release with less cellular toxicity. Notably, HT-7 increased cell surface BST2 coupled with HIV-1 release reduction in Jurkat cells but not Jurkat/KO-BST2 cells. Seemingly, HT-7 impeded simian immunodeficiency virus (SIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) release. Concisely, these results suggest that the reduction in viral release, following HT-7 treatment, resulted from the modulation of cell surface expression of BST2 by HT-7.","journal":"Journal of Biological Chemistry","year":2024,"id":477376,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9454,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1315644,"name":"Akihiro Togami","orcid":null,"position":1,"is_corresponding":false},{"id":1315645,"name":"Tomofumi Yoshida","orcid":null,"position":2,"is_corresponding":false},{"id":1315135,"name":"Takuya Masunaga","orcid":"0000-0002-5774-3820","position":3,"is_corresponding":false},{"id":1315646,"name":"MST Monira Begum","orcid":null,"position":4,"is_corresponding":false},{"id":1315647,"name":"Hiromi Terasawa","orcid":null,"position":5,"is_corresponding":false},{"id":1315648,"name":"Nami Monde","orcid":null,"position":6,"is_corresponding":false},{"id":1315649,"name":"Yurika Tahara","orcid":null,"position":7,"is_corresponding":false},{"id":1146687,"name":"Reiko Tanaka","orcid":"0000-0002-0769-9382","position":8,"is_corresponding":false},{"id":1315136,"name":"Yuetsu Tanaka","orcid":"0000-0002-4845-2810","position":9,"is_corresponding":false},{"id":1315650,"name":"Joyce Appiah-Kubi","orcid":null,"position":10,"is_corresponding":false},{"id":1315651,"name":"Wright Andrews Ofotsu Amesimeku","orcid":null,"position":11,"is_corresponding":false},{"id":1315137,"name":"Md Jakir Hossain","orcid":"0000-0003-4924-8982","position":12,"is_corresponding":false},{"id":1315138,"name":"Masami Otsuka","orcid":"0000-0002-2968-3939","position":13,"is_corresponding":false},{"id":616897,"name":"Kazuhisa Yoshimura","orcid":null,"position":14,"is_corresponding":false},{"id":615281,"name":"Terumasa Ikeda","orcid":"0000-0003-2869-9450","position":15,"is_corresponding":false},{"id":1241481,"name":"Tomohiro Sawa","orcid":"0000-0002-7949-7309","position":16,"is_corresponding":false},{"id":1235995,"name":"Yorifumi Satou","orcid":"0000-0002-1495-7810","position":17,"is_corresponding":false},{"id":1315139,"name":"Mikako Fujita","orcid":"0000-0001-6705-4052","position":18,"is_corresponding":false},{"id":1315140,"name":"Yosuke Maeda","orcid":"0000-0001-6441-4067","position":19,"is_corresponding":false},{"id":1315141,"name":"Hiroshi Tateishi","orcid":"0000-0003-1225-0720","position":20,"is_corresponding":false},{"id":1315142,"name":"Kazuaki Monde","orcid":"0000-0002-8314-5306","position":21,"is_corresponding":false},{"id":1315643,"name":"Perpetual Nyame","orcid":null,"position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-19T02:06:33.741984Z","pmid":"39173946","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}