{"doi":"10.1128/aac.00462-23","title":"Biological and Structural Analyses of New Potent Allosteric Inhibitors of HIV-1 Integrase","abstract":"HIV-1 integrase-LEDGF allosteric inhibitors (INLAIs) share the binding site on the viral protein with the host factor LEDGF/p75. These small molecules act as molecular glues promoting hyper-multimerization of HIV-1 IN protein to severely perturb maturation of viral particles. Herein, we describe a new series of INLAIs based on a benzene scaffold that display antiviral activity in the single digit nanomolar range. Akin to other compounds of this class, the INLAIs predominantly inhibit the late stages of HIV-1 replication. A series of high-resolution crystal structures revealed how these small molecules engage the catalytic core and the C-terminal domains of HIV-1 IN. No antagonism was observed between our lead INLAI compound BDM-2 and a panel of 16 clinical antiretrovirals. Moreover, we show that compounds retained high antiviral activity against HIV-1 variants resistant to IN strand transfer inhibitors and other classes of antiretroviral drugs. The virologic profile of BDM-2 and the recently completed single ascending dose phase I trial (ClinicalTrials.gov identifier: NCT03634085) warrant further clinical investigation for use in combination with other antiretroviral drugs. Moreover, our results suggest routes for further improvement of this emerging drug class.","journal":"Antimicrobial Agents and Chemotherapy","year":2023,"id":342815,"datarank":0.553807518957697,"base_score":2.70805020110221,"endowment":2.70805020110221,"self_citation_contribution":0.40620753016533157,"citation_network_contribution":0.14759998879236547,"self_endowment_contribution":0.40620753016533157,"citer_contribution":0.14759998879236547,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":11,"citers_with_citation_signal":7,"citers_with_endowment":7,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9463,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT03634085"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1080344,"name":"Erwann Le Rouzic","orcid":null,"position":1,"is_corresponding":false},{"id":1068268,"name":"Matthew R. Singer","orcid":null,"position":2,"is_corresponding":false},{"id":450804,"name":"Zhe Yu","orcid":"0000-0002-6908-6135","position":3,"is_corresponding":false},{"id":1080345,"name":"Frédéric Le Strat","orcid":null,"position":4,"is_corresponding":false},{"id":1079819,"name":"Claire Batisse","orcid":"0000-0003-3064-6569","position":5,"is_corresponding":false},{"id":767951,"name":"Julien Batisse","orcid":"0000-0003-1285-1083","position":6,"is_corresponding":false},{"id":1079820,"name":"Céline Amadori","orcid":"0000-0002-2958-6098","position":7,"is_corresponding":false},{"id":1080346,"name":"Sophie Chasset","orcid":null,"position":8,"is_corresponding":false},{"id":626565,"name":"Valerie E. Pye","orcid":"0000-0001-9616-2992","position":9,"is_corresponding":false},{"id":321016,"name":"Stéphane Emiliani","orcid":"0000-0001-7344-8429","position":10,"is_corresponding":false},{"id":1080347,"name":"Benoît Ledoussal","orcid":null,"position":11,"is_corresponding":false},{"id":1079821,"name":"Marc Ruff","orcid":"0000-0001-5451-6377","position":12,"is_corresponding":false},{"id":571180,"name":"F. Moreau","orcid":"0000-0003-4217-8264","position":13,"is_corresponding":false},{"id":277729,"name":"Peter Cherepanov","orcid":"0000-0002-0634-538X","position":14,"is_corresponding":false},{"id":1079822,"name":"Richard Benarous","orcid":"0000-0003-0242-2816","position":15,"is_corresponding":false},{"id":1079818,"name":"Damien Bonnard","orcid":"0000-0001-9529-5785","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T01:11:17.288563Z","pmid":"37310224","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":[]}