biostudies-literatureKhalek ISDBT/Wellcome Trust India AllianceWellcome Trusteadk1867https://www.ebi.ac.uk/biostudies/studies/S-EPMC7617732biostudies-literatureUnknown16(735)Snakebite envenoming is a major global public health concern for which improved therapies are urgently needed. The antigenic diversity present in snake venom toxins from various species presents a considerable challenge to the development of a universal antivenom. Here, we used a synthetic human antibody library to find and develop an antibody that neutralizes long-chain three-finger α-neurotoxins produced by numerous medically relevant snakes. Our antibody bound diverse toxin variants with high affinity, blocked toxin binding to the nicotinic acetylcholine receptor in vitro, and protected mice from lethal venom challenge. Structural analysis of the antibody-toxin complex revealed a binding mode that mimics the receptor-toxin interaction. The overall workflow presented is generalizable forScience translational medicineSynthetic development of a broadly neutralizing antibody against snake venom long-chain α-neurotoxins.PMC7617732223619221705/Z/20/ZIA/I/19/2/504647223619/Z/21/ZJardine JGCasewell NRMenzies SKSunagar KNguyen YTKSaye-Francisco KBurton DRKedzior MSok DLimbo OStanfield RLMisson Mindrebo LSmith JMWilson IAVerma MKhochare SSenji Laxme RRHarrison RAKhalek ISWoehl JBore ETran QKim YPatel RNAinsworth SfalseSynthetic development of a broadly neutralizing antibody against snake venom long-chain α-neurotoxins.Snakebite envenoming is a major global public health concern for which improved therapies are urgently needed. The antigenic diversity present in snake venom toxins from various species presents a considerable challenge to the development of a universal antivenom. Here, we used a synthetic human antibody library to find and develop an antibody that neutralizes long-chain three-finger α-neurotoxins produced by numerous medically relevant snakes. Our antibody bound diverse toxin variants with high affinity, blocked toxin binding to the nicotinic acetylcholine receptor in vitro, and protected mice from lethal venom challenge. Structural analysis of the antibody-toxin complex revealed a binding mode that mimics the receptor-toxin interaction. The overall workflow presented is generalizable for2024-01-01T00:00:00Z2024 Feb2026-04-08T19:14:01.12Z2026-04-08T12:01:24.572ZS-EPMC76177323838184710.1126/scitranslmed.adk1867