{"doi":"10.1016/j.mcpro.2024.100901","title":"Molecular Display of the Animal Meta-Venome for Discovery of Novel Therapeutic Peptides","abstract":"Animal venoms, distinguished by their unique structural features and potent bioactivities, represent a vast and relatively untapped reservoir of therapeutic molecules. However, limitations associated with comprehensively constructing and expressing highly complex venom and venom-like molecule libraries have precluded their therapeutic evaluation via high-throughput screening. Here, we developed an innovative computational approach to design a highly diverse library of animal venoms and \"metavenoms\". We used programmable M13 hyperphage display to preserve critical disulfide-bonded structures for highly parallelized single-round biopanning with quantitation via high-throughput DNA sequencing. Our approach led to the discovery of Kunitz-type domain containing proteins that target the human itch receptor Mas-related G-protein coupled receptor member X4, which plays a crucial role in itch perception. Deep learning-based structural homology mining identified two endogenous human homologs, tissue factor pathway inhibitor (TFPI), and serine peptidase inhibitor, Kunitz type 2 (SPINT2), which exhibit agonist-dependent potentiation of Mas-related G-protein coupled receptor member X4. Highly multiplexed screening of animal venoms and metavenoms is therefore a promising approach to uncover new drug candidates.","journal":"Molecular & Cellular Proteomics","year":2024,"id":461837,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9566,"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":1290799,"name":"Yang Miao","orcid":"0000-0002-4127-2980","position":1,"is_corresponding":false},{"id":1290800,"name":"Zixing Liu","orcid":"0009-0004-4960-2579","position":2,"is_corresponding":false},{"id":56797,"name":"Konstantin Schütze","orcid":"0000-0002-3957-412X","position":3,"is_corresponding":false},{"id":297463,"name":"Nathachit Limjunyawong","orcid":"0000-0002-9540-6171","position":4,"is_corresponding":false},{"id":664742,"name":"Daphne Chun-Che Chien","orcid":"0000-0001-6844-5477","position":5,"is_corresponding":false},{"id":1291317,"name":"Wayne Denis Monteiro","orcid":null,"position":6,"is_corresponding":false},{"id":983303,"name":"Lee‐Shin Chu","orcid":"0000-0001-8315-642X","position":7,"is_corresponding":false},{"id":555588,"name":"William R. Morgenlander","orcid":"0000-0001-7205-3732","position":8,"is_corresponding":false},{"id":808762,"name":"Sahana Jayaraman","orcid":"0000-0003-3413-2530","position":9,"is_corresponding":false},{"id":1291318,"name":"Sung-eun Jang","orcid":null,"position":10,"is_corresponding":false},{"id":242226,"name":"Jeffrey J. Gray","orcid":"0000-0001-6380-2324","position":11,"is_corresponding":false},{"id":1290801,"name":"Heng Zhu","orcid":"0000-0002-8408-3821","position":12,"is_corresponding":false},{"id":297467,"name":"Xinzhong Dong","orcid":"0000-0002-9750-7718","position":13,"is_corresponding":false},{"id":32517,"name":"Martin Steinegger","orcid":"0000-0001-8781-9753","position":14,"is_corresponding":false},{"id":108428,"name":"H. Benjamin Larman","orcid":"0000-0001-7863-196X","position":15,"is_corresponding":false},{"id":1143533,"name":"Meng-Hsuan Hsiao","orcid":"0000-0002-3190-7081","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:04:16.410510Z","pmid":"39746545","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":[]}