{"doi":"10.3390/ijms22179308","title":"High-Throughput NanoBiT-Based Screening for Inhibitors of HIV-1 Vpu and Host BST-2 Protein Interaction","abstract":"Bone marrow stromal cell antigen 2 (BST-2), also known as CD317 or tetherin, has been identified as a host restriction factor that suppresses the release of enveloped viruses from host cells by physically tethering viral particles to the cell surface; however, this host defense can be subverted by multiple viruses. For example, human immunodeficiency virus (HIV)-1 encodes a specific accessory protein, viral protein U (Vpu), to counteract BST-2 by binding to it and directing its lysosomal degradation. Thus, blocking the interaction between Vpu and BST-2 will provide a promising strategy for anti-HIV therapy. Here, we report a NanoLuc Binary Technology (NanoBiT)-based high-throughput screening assay to detect inhibitors that disrupt the Vpu-BST-2 interaction. Out of more than 1000 compounds screened, four inhibitors were identified with strong activity at nontoxic concentrations. In subsequent cell-based BST-2 degradation assays, inhibitor Y-39983 HCl restored the cell-surface and total cellular level of BST-2 in the presence of Vpu. Furthermore, the Vpu-mediated enhancement of pesudotyped viral particle production was inhibited by Y-39983 HCl. Our findings indicate that our newly developed assay can be used for the discovery of potential antiviral molecules with novel mechanisms of action.","journal":"International Journal of Molecular Sciences","year":2021,"id":184564,"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":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9587,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":693713,"name":"Xiaoxiao Dong","orcid":"0009-0000-0703-253X","position":1,"is_corresponding":false},{"id":739813,"name":"Wenmei Zhang","orcid":"0000-0003-1658-7582","position":2,"is_corresponding":false},{"id":284488,"name":"Tian Chen","orcid":"0000-0003-2900-9087","position":3,"is_corresponding":false},{"id":739814,"name":"Boyang Yu","orcid":"0000-0002-1401-9250","position":4,"is_corresponding":false},{"id":739815,"name":"Wenyue Zhao","orcid":"0000-0002-1982-1074","position":5,"is_corresponding":false},{"id":739816,"name":"Yishu Yang","orcid":"0009-0003-7231-0171","position":6,"is_corresponding":false},{"id":379144,"name":"Xiaoli Wang","orcid":"0000-0003-4569-5371","position":7,"is_corresponding":false},{"id":739817,"name":"Qin Hu","orcid":"0000-0003-1196-879X","position":8,"is_corresponding":false},{"id":739818,"name":"Xiayan Wang","orcid":"0000-0003-1735-0077","position":9,"is_corresponding":false},{"id":739812,"name":"Boye Li","orcid":"0000-0002-1923-4013","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-18T23:48:30.970730Z","pmid":"34502213","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":[]}