{"doi":"10.1126/scitranslmed.adk4802","title":"Molecular dissection of cobra venom highlights heparinoids as an antidote for spitting cobra envenoming","abstract":"Snakebites affect about 1.8 million people annually. The current standard of care involves antibody-based antivenoms, which can be difficult to access and are generally not effective against local tissue injury, the primary cause of morbidity. Here, we used a pooled whole-genome CRISPR knockout screen to define human genes that, when targeted, modify cell responses to spitting cobra venoms. A large portion of modifying genes that conferred resistance to venom cytotoxicity was found to control proteoglycan biosynthesis, including <i>EXT1</i>, <i>B4GALT7</i>, <i>EXT2</i>, <i>EXTL3</i>, <i>XYLT2</i>, <i>NDST1</i>, and <i>SLC35B2</i>, which we validated independently. This finding suggested heparinoids as possible inhibitors. Heparinoids prevented venom cytotoxicity through binding to three-finger cytotoxins, and the US Food and Drug Administration-approved heparinoid tinzaparin was found to reduce tissue damage in mice when given via a medically relevant route and dose. Overall, our systematic molecular dissection of cobra venom cytotoxicity provides insight into how we can better treat cobra snakebite envenoming.","journal":"Science Translational Medicine","year":2024,"id":9142,"datarank":0.3958585994422889,"base_score":2.639057329615259,"endowment":2.639057329615259,"self_citation_contribution":0.3958585994422889,"citation_network_contribution":0.0,"self_endowment_contribution":0.3958585994422889,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0464,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-07-17","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":78299,"name":"Steven R. Hall","orcid":"0000-0001-5314-4970","position":1,"is_corresponding":false},{"id":78300,"name":"Felicity Chung","orcid":null,"position":2,"is_corresponding":false},{"id":78301,"name":"Sergey Kurdyukov","orcid":"0000-0001-5824-0443","position":3,"is_corresponding":false},{"id":78302,"name":"Edouard Crittenden","orcid":"0000-0003-1676-5457","position":4,"is_corresponding":false},{"id":78303,"name":"Karishma Patel","orcid":"0000-0003-3034-3840","position":5,"is_corresponding":false},{"id":78304,"name":"Charlotte A. Dawson","orcid":"0000-0003-3922-9518","position":6,"is_corresponding":false},{"id":78305,"name":"Adam P. Westhorpe","orcid":"0000-0002-7499-9174","position":7,"is_corresponding":false},{"id":78306,"name":"Keirah E. Bartlett","orcid":"0000-0003-3497-1385","position":8,"is_corresponding":false},{"id":78307,"name":"Sean A. Rasmussen","orcid":"0000-0002-3231-0404","position":9,"is_corresponding":false},{"id":78308,"name":"Cesar L. Moreno","orcid":"0000-0002-0876-0341","position":10,"is_corresponding":false},{"id":78309,"name":"Christopher E. Denes","orcid":"0000-0002-8669-8088","position":11,"is_corresponding":false},{"id":78310,"name":"Laura-Oana Albulescu","orcid":"0000-0001-6563-9217","position":12,"is_corresponding":false},{"id":78311,"name":"Amy E. Marriott","orcid":"0000-0002-4806-9539","position":13,"is_corresponding":false},{"id":78312,"name":"Joel P. Mackay","orcid":"0000-0001-7508-8033","position":14,"is_corresponding":false},{"id":78313,"name":"Mark C. Wilkinson","orcid":"0000-0003-3109-6888","position":15,"is_corresponding":false},{"id":78314,"name":"José Marı́a Gutiérrez","orcid":"0000-0001-8385-3081","position":16,"is_corresponding":false},{"id":78315,"name":"Nicholas R. Casewell","orcid":"0000-0002-8035-4719","position":17,"is_corresponding":false},{"id":78316,"name":"G. Gregory Neely","orcid":"0000-0002-1957-9732","position":18,"is_corresponding":false},{"id":78298,"name":"Tian Y. Du","orcid":"0000-0002-0674-361X","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-03-01T18:20:47.508186Z","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":[]}