02137nas a2200433   4500000000100000008004100001260006300042653002100105653002500126100001400151700001900165700001500184700001500199700001300214700001200227700001300239700002100252700001000273700002200283700001100305700001500316700001200331700001200343700001200355700001700367700001500384700001600399700001600415700001400431700001000445700001400455700001600469700001400485700001500499245010700514490000700621520105000628022002501678       2024                            d  bAmerican Association for the Advancement of Science (AAAS)10aGeneral Medicine10asnakebite envenoming1 aKhalek IS1 aSenji Laxme RR1 aNguyen YTK1 aKhochare S1 aPatel RN1 aWoehl J1 aSmith JM1 aSaye-Francisco K1 aKim Y1 aMisson Mindrebo L1 aTran Q1 aKędzior M1 aBoré E1 aLimbo O1 aVerma M1 aStanfield RL1 aMenzies SK1 aAinsworth S1 aHarrison RA1 aBurton DR1 aSok D1 aWilson IA1 aCasewell NR1 aSunagar K1 aJardine JG00aSynthetic development of a broadly neutralizing antibody against snake venom long-chain α-neurotoxins0 v163 a<p>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.</p>
  a1946-6234, 1946-6242