{"doi":"10.17615/n86s-9922","title":"IgG Fc-binding motif-conjugated HIV-1 fusion inhibitor exhibits improved potency and in vivo half-life: Potential application in combination with broad neutralizing antibodies","abstract":"The clinical application of conventional peptide drugs, such as the HIV-1 fusion inhibitor enfuvirtide, is limited by their short half-life in vivo. To overcome this limitation, we developed a new strategy to extend the in vivo half-life of a short HIV-1 fusion inhibitory peptide, CP24, by fusing it with the human IgG Fc-binding peptide (IBP). The newly engineered peptide IBPCP24 exhibited potent and broad anti-HIV-1 activity with IC50 values ranging from 0.2 to 173.7 nM for inhibiting a broad spectrum of HIV-1 strains with different subtypes and tropisms, including those resistant to enfuvirtide. Most importantly, its half-life in the plasma of rhesus monkeys was 46.1 h, about 26- and 14-fold longer than that of CP24 (t1/2 = 1.7 h) and enfuvirtide (t1/2 = 3 h), respectively. IBP-CP24 intravenously administered in rhesus monkeys could not induce significant IBP-CP24-specific antibody response and it showed no obvious in vitro or in vivo toxicity. In the prophylactic study, humanized mice pretreated with IBPCP24 were protected from HIV-1 infection. As a therapeutic treatment, coadministration of IBP-CP24 and normal human IgG to humanized mice with chronic HIV-1 infection resulted in a significant decrease of plasma viremia. Combining IBP-CP24 with a broad neutralizing antibody (bNAb) targeting CD4-binding site (CD4bs) in gp120 or a membrane proximal external region (MPER) in gp41 exhibited synergistic effect, resulting in significant dose-reduction of the bNAb and IBP-CP24. These results suggest that IBP-CP24 has the potential to be further developed as a new HIV-1 fusion inhibitor-based, long-acting anti-HIV drug that can be used alone or in combination with a bNAb for treatment and prevention of HIV-1 infection.","journal":"UNC Libraries","year":2020,"id":134951,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9486,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":537939,"name":"Guangming Li","orcid":"0000-0003-2286-7679","position":1,"is_corresponding":false},{"id":226306,"name":"Qian Wang","orcid":"0000-0001-5504-0008","position":2,"is_corresponding":false},{"id":522303,"name":"Wei Xu","orcid":"0000-0002-1960-0992","position":3,"is_corresponding":false},{"id":237956,"name":"Lu Lu","orcid":"0000-0002-2255-0391","position":4,"is_corresponding":false},{"id":255662,"name":"Lishan Su","orcid":"0000-0002-0350-5560","position":5,"is_corresponding":false},{"id":590499,"name":"Wenwen Bi","orcid":"0000-0002-2960-441X","position":6,"is_corresponding":false},{"id":590500,"name":"Liang Cheng","orcid":"0000-0003-4105-1763","position":7,"is_corresponding":false},{"id":105107,"name":"Shibo Jiang","orcid":"0000-0001-8283-7135","position":8,"is_corresponding":false},{"id":590501,"name":"Qi Wang","orcid":"0000-0002-1941-5287","position":9,"is_corresponding":false},{"id":591313,"name":"Xue, Jing","orcid":null,"position":10,"is_corresponding":false},{"id":237951,"name":"Shuai Xia","orcid":"0000-0001-7896-4182","position":11,"is_corresponding":false},{"id":7613,"name":"Chuan Qin","orcid":"0000-0002-6261-1232","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:16:27.963294Z","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":[]}