@article{99681, keywords = {General Medicine, snakebite envenoming}, author = {Khalek IS and Senji Laxme RR and Nguyen YTK and Khochare S and Patel RN and Woehl J and Smith JM and Saye-Francisco K and Kim Y and Misson Mindrebo L and Tran Q and Kędzior M and Boré E and Limbo O and Verma M and Stanfield RL and Menzies SK and Ainsworth S and Harrison RA and Burton DR and Sok D and Wilson IA and Casewell NR and Sunagar K and Jardine JG}, title = {Synthetic development of a broadly neutralizing antibody against snake venom long-chain α-neurotoxins}, abstract = {

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 for the development of antibodies that target conserved epitopes among antigenically diverse targets, and it offers a promising framework for the creation of a monoclonal antibody–based universal antivenom to treat snakebite envenoming.

}, year = {2024}, journal = {Science Translational Medicine}, volume = {16}, publisher = {American Association for the Advancement of Science (AAAS)}, issn = {1946-6234, 1946-6242}, doi = {10.1126/scitranslmed.adk1867}, language = {Eng}, }