{"doi":"10.3390/v17040514","title":"Design and Characterization of Inhibitors of Cell-Mediated Degradation of APOBEC3G That Decrease HIV-1 Infectivity","abstract":"The cytoplasmic human Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3 or A3) cytidine deaminases G and F (A3G and A3F) can block the spread of human immunodeficiency virus (HIV). HIV counteracts this cell-intrinsic defense through a viral protein called viral infectivity factor (Vif). Vif causes proteasomal degradation of A3G and A3F proteins (A3G/F) in HIV-producing cells to ensure infectivity of virions subsequently released from these cells. Here, we optimized a lead compound reported previously to boost cellular levels of A3G. The modified analogs designed, synthesized, and evaluated here inhibit cell-mediated post-translational degradation of A3G/F, whether Vif is present or not. This increases A3G/F incorporation into Vif-positive virions to decrease viral infectivity. The compounds and processes described here can facilitate the development of new anti-HIV therapeutics whose host-targeted effect may not be evaded by resistance-conferring mutations in HIV Vif.","journal":"Viruses","year":2025,"id":552211,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9583,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":738356,"name":"Cristina C. Vaca","orcid":"0000-0002-1457-0990","position":1,"is_corresponding":false},{"id":1448389,"name":"Neha Malik","orcid":"0000-0002-8339-7546","position":2,"is_corresponding":false},{"id":329246,"name":"Isabelle Clerc","orcid":"0000-0002-7140-7049","position":3,"is_corresponding":false},{"id":1448390,"name":"Joshua Craft","orcid":"0009-0007-8676-224X","position":4,"is_corresponding":false},{"id":329245,"name":"Hannah Hudson","orcid":"0000-0001-5688-8182","position":5,"is_corresponding":false},{"id":739088,"name":"Gaël K. Scholtés","orcid":null,"position":6,"is_corresponding":false},{"id":242018,"name":"Gary E. Schiltz","orcid":"0000-0003-4180-5051","position":7,"is_corresponding":false},{"id":257031,"name":"Meejeon Roh","orcid":null,"position":8,"is_corresponding":false},{"id":739089,"name":"Chisu Song","orcid":null,"position":9,"is_corresponding":false},{"id":329248,"name":"Richard T. D’Aquila","orcid":"0000-0002-9653-5987","position":10,"is_corresponding":false},{"id":738355,"name":"Aubrey M. Sawyer","orcid":"0000-0003-0862-2237","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T02:54:33.203144Z","pmid":"40284957","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":[]}