{"doi":"10.1101/2024.02.28.582529","title":"Next Generation Neuropeptide Y Receptor Small Molecule Agonists Inhibit Mosquito Biting Behavior","abstract":"Abstract Female Aedes aegypti mosquitoes can spread disease-causing pathogens when they bite humans to obtain blood nutrients required for egg production. Following a complete blood meal, host-seeking is suppressed until eggs are laid. Neuropeptide Y-like Receptor 7 (NPYLR7) plays a role in endogenous host-seeking suppression and previous work identified small molecule NPYLR7 agonists that suppress host-seeking and blood feeding when fed to mosquitoes at high micromolar doses. Using structure activity relationship analysis and structure-guided design we synthesized 128 compounds with similarity to known NPYLR7 agonists. Although in vitro potency (EC 50 ) was not strictly predictive of in vivo effect, we identified 3 compounds that suppressed blood feeding from a live host when fed to mosquitoes at a 1 μM dose, a 100-fold improvement over the original reference compound. Exogenous activation of NPYLR7 represents an innovative vector control strategy to block mosquito biting behavior and prevent mosquito/human host interactions that lead to pathogen transmission.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":485968,"datarank":0.26007899759634096,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.018663310731225857,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.018663310731225857,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":4,"citers_with_citation_signal":2,"citers_with_endowment":2,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9482,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":40797,"name":"Leigh A. Baxt","orcid":"0000-0001-8286-3907","position":1,"is_corresponding":false},{"id":1251179,"name":"Tanweer A. Khan","orcid":"0000-0001-9270-9831","position":2,"is_corresponding":false},{"id":611060,"name":"Mayako Michino","orcid":"0000-0002-5469-025X","position":3,"is_corresponding":false},{"id":1329454,"name":"Michael Miller","orcid":"0000-0001-7990-3381","position":4,"is_corresponding":false},{"id":718989,"name":"David J. Huggins","orcid":"0000-0003-1579-2496","position":5,"is_corresponding":false},{"id":410893,"name":"Caroline S. Jiang","orcid":"0000-0001-6765-6280","position":6,"is_corresponding":false},{"id":267007,"name":"Leslie B. Vosshall","orcid":"0000-0002-6060-8099","position":7,"is_corresponding":false},{"id":376579,"name":"Laura B. Duvall","orcid":"0000-0002-1821-6809","position":8,"is_corresponding":false},{"id":846769,"name":"Emely V. Zeledon","orcid":"0000-0002-0365-6019","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:07:57.049469Z","pmid":"38464241","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":[]}