{"doi":"10.3389/fphar.2020.613361","title":"Rational Design of A Novel Small-Molecule HIV-1 Inactivator Targeting Both gp120 and gp41 of HIV-1","abstract":"Virus inactivator can inactivate cell-free virions without relying on their replication cycle, potentially reducing the impact of viral infection on cells. Previously, we successfully constructed a HIV-1 protein inactivator, 2DLT, by conjugating the D1D2 region of CD4 to the fusion inhibitor T1144 via a 35-amino acid linker. Therefore, it targets both the CD4 binding site in gp120 and NHR region in gp41. Considering that small-molecule agents have the advantages of fast production, low cost, good stability, and oral availability, we herein report the design of a new small-molecule HIV-1 inactivator, FD028, by conjugating FD016 (an analog of NBD-556, a gp120-CD4 binding inhibitor) with FD017 (an analog of 11d, an HIV-1 fusion inhibitor). The results showed that FD028 inactivated cell-free virions at a moderate nanomolar concentration by targeting both HIV-1 gp120 and gp41. Moreover, FD028 has broad-spectrum inhibition and inactivation activity against HIV-1 resistant strains and primary isolates of different subtypes without significant cytotoxicity. Therefore, FD028 has potential for further development as an HIV-1 inactivator-based therapeutic.","journal":"Frontiers in Pharmacology","year":2021,"id":198175,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9492,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":94204,"name":"Yu Dai","orcid":"0000-0002-7432-226X","position":1,"is_corresponding":false},{"id":772816,"name":"Qian Wang","orcid":"0000-0001-5322-0283","position":2,"is_corresponding":false},{"id":237956,"name":"Lu Lu","orcid":"0000-0002-2255-0391","position":3,"is_corresponding":false},{"id":772817,"name":"Junqi Zhang","orcid":"0009-0001-4733-023X","position":4,"is_corresponding":false},{"id":237952,"name":"Wei Xu","orcid":"0000-0003-3013-7182","position":5,"is_corresponding":false},{"id":519381,"name":"Lan Xie","orcid":"0000-0001-5831-8730","position":6,"is_corresponding":false},{"id":772818,"name":"Shengqi Wang","orcid":"0000-0001-8100-7295","position":7,"is_corresponding":false},{"id":311123,"name":"Fei Yu","orcid":"0000-0001-6332-4326","position":8,"is_corresponding":false},{"id":772819,"name":"Xiaoyang He","orcid":"0000-0003-0958-5108","position":9,"is_corresponding":false},{"id":105107,"name":"Shibo Jiang","orcid":"0000-0001-8283-7135","position":10,"is_corresponding":false},{"id":105105,"name":"Jing Pu","orcid":"0000-0002-1851-8583","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-18T23:50:27.616568Z","pmid":"33569006","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":[]}