{"doi":"10.1016/j.jmb.2006.09.017","title":"Synergistic Inhibition of HIV-1 Envelope-Mediated Membrane Fusion by Inhibitors Targeting the N and C-Terminal Heptad Repeats of gp41","abstract":null,"journal":"Journal of Molecular Biology","year":2006,"id":606214,"datarank":0.48283137373023016,"base_score":3.2188758248682006,"endowment":3.2188758248682006,"self_citation_contribution":0.48283137373023016,"citation_network_contribution":0.0,"self_endowment_contribution":0.48283137373023016,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":458319,"name":"John M. Louis","orcid":"0000-0002-0052-1899","position":1,"is_corresponding":false},{"id":383504,"name":"Carole A. Bewley","orcid":"0000-0003-2203-0852","position":2,"is_corresponding":false},{"id":57566,"name":"G. Marius Clore","orcid":"0000-0003-3809-1027","position":3,"is_corresponding":false},{"id":1402709,"name":"Elena Gustchina","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Synergistic Inhibition of HIV-1 Envelope-Mediated Membrane Fusion by Inhibitors Targeting the N and C-Terminal Heptad Repeats of gp41","abstract":"The human immunodeficiency virus type-1 (HIV-1) envelope (Env) proteins that mediate membrane fusion represent a major target for the development of new AIDS therapies. Three classes of Env-mediated membrane fusion inhibitors have been described that specifically target the pre-hairpin intermediate conformation of gp41. Class 2 inhibitors bind to the C-terminal heptad repeat (C-HR) of gp41. The single example of a class 3 inhibitor targets the trimeric N-terminal heptad repeat (N-HR) of gp41 and has been postulated to sequestrate the N-HR of the pre-hairpin intermediate through the formation of fusion incompetent heterotrimers. Here, we show that N(CCG)-gp41, a class 2 inhibitor, and N36(Mut(e,g)), a class 3 inhibitor, synergistically inhibit Env-mediated membrane fusion for several representative HIV-1 strains (X4 and R5) in both a cell fusion assay (with membrane-bound CD4) and an Env-pseudo-typed virus neutralization assay. The mechanistic, as well as potential therapeutic, implications of these observations for HIV-Env-mediated membrane fusion are discussed.","is_dataset_classified":null,"base_score":3.2188758248682006,"endowment":3.2188758248682006,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"17010381","pmcid":"PMC1785329","openalex_id":"https://openalex.org/W2024164841","authors":[],"funders":[{"funder_name":"NIDDK NIH HHS","grant_id":"Z01 DK029023-15","title":null},{"funder_name":"National Institute of Diabetes and Digestive and Kidney Diseases","grant_id":"","title":null},{"funder_name":"Intramural NIH HHS","grant_id":"","title":null},{"funder_name":"National Institutes of Health","grant_id":"","title":null},{"funder_name":"Intramural NIH HHS","grant_id":"","title":null}],"total_grants":5,"fwci":0.8636,"citation_percentile":0.67238002,"influential_citations":0,"citation_trend":[{"year":2012,"count":2},{"year":2015,"count":2},{"year":2016,"count":1},{"year":2017,"count":4},{"year":2019,"count":2},{"year":2022,"count":2}],"oa_status":"green","license":"https://www.elsevier.com/legal/tdmrep-license","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1785329","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1785329","host_type":"repository"},{"url":"https://api.elsevier.com/content/article/PII:S002228360601206X?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S002228360601206X?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.jmb.2006.09.017","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/17010381","host_type":"repository"}],"fields_of_study":["HIV Research and Treatment","HIV/AIDS drug development and treatment","RNA and protein synthesis mechanisms","Amino Acid Motifs","Amino Acid Sequence","Animals","Cell Line","Drug Synergism","HIV Envelope Protein gp41","HIV Fusion Inhibitors","HIV-1","Humans","Membrane Fusion","Molecular Sequence Data","Peptides","Protein Conformation"],"mesh_terms":["Amino Acid Sequence","Animals","Cell Line","Drug Synergism","Humans","Membrane Fusion","Molecular Sequence Data","Peptides","Protein Conformation","HIV-1","HIV Envelope Protein gp41","Amino Acid Motifs","HIV Fusion Inhibitors"],"keywords":["Gp41","Heptad repeat","Human immunodeficiency virus (HIV)","Membrane","Terminal (telecommunication)","Lipid bilayer fusion","Fusion","Chemistry","Envelope (radar)","Biology","Virology","Cell biology","Biochemistry","Genetics","Peptide sequence","Computer science","Antibody","Epitope","Gene"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-30T04:06:37.990062Z","pmid":null,"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":[]}