{"doi":"10.3390/ph15040424","title":"A Protein-Based, Long-Acting HIV-1 Fusion Inhibitor with an Improved Pharmacokinetic Profile","abstract":"Recently, a series of highly effective peptide- or protein-based HIV fusion inhibitors have been identified. However, due to their short half-life, their clinical application is limited. Therefore, the development of long-acting HIV fusion inhibitors is urgently needed. Here, we designed and constructed a protein-based, long-acting HIV fusion inhibitor, termed FLT (FN3-L35-T1144), consisting of a monobody, FN3, which contains an albumin-binding domain (ABD), a 35-mer linker (L35), and a peptide-based HIV fusion inhibitor, T1144. We found that FLT bound, via its FN3 component, with human serum albumin (HSA) in a reversible manner, thus maintaining the high efficiency of T1144 against infection by both HIV-1 IIIB (X4) and Bal (R5) strains with IC50 of 11.6 nM and 15.3 nM, respectively, and remarkably prolonging the half-life of T1144 (~27 h in SD rats). This approach affords protein-based HIV fusion inhibitors with much longer half-life compared to enfuvirtide, a peptide-based HIV fusion inhibitor approved for use in clinics. Therefore, FLT is a promising candidate as a new protein-based anti-HIV drug with an improved pharmacokinetic profile.","journal":"Pharmaceuticals","year":2022,"id":286123,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9475,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":965494,"name":"Zhe Cong","orcid":null,"position":1,"is_corresponding":false},{"id":965495,"name":"Qianyu Duan","orcid":null,"position":2,"is_corresponding":false},{"id":772816,"name":"Qian Wang","orcid":"0000-0001-5322-0283","position":3,"is_corresponding":false},{"id":535558,"name":"Shan Su","orcid":"0000-0003-0593-9968","position":4,"is_corresponding":false},{"id":898534,"name":"Rui Wang","orcid":"0000-0001-7209-741X","position":5,"is_corresponding":false},{"id":237956,"name":"Lu Lu","orcid":"0000-0002-2255-0391","position":6,"is_corresponding":false},{"id":965054,"name":"Jing Xue","orcid":"0000-0002-9113-2433","position":7,"is_corresponding":false},{"id":105107,"name":"Shibo Jiang","orcid":"0000-0001-8283-7135","position":8,"is_corresponding":false},{"id":237952,"name":"Wei Xu","orcid":"0000-0003-3013-7182","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T00:29:48.841035Z","pmid":"35455421","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":[]}