De novo designed proteins neutralize lethal snake venom toxins

Snakebite envenoming remains a devastating and neglected tropical disease, claiming over 100,000 lives annually and causing severe complications and long-lasting disabilities for many more1,2. Three-finger toxins (3FTx) are highly toxic components of elapid snake venoms that can cause diverse pathologies, including severe tissue damage3 and inhibition of nicotinic acetylcholine receptors, resulting in life-threatening neurotoxicity4. At present, the only available treatments for snakebites consist of polyclonal antibodies derived from the plasma of immunized animals, which have high cost and limited efficacy against 3FTxs5–7. Here we used deep learning methods to de novo design proteins to bind short-chain and…

• NS
  National Science Foundation

  Awards: P30GM133893, 2307044, DE-SC0012704
• UD
  U.S. Department of Energy

  Awards: KP1607011, SC0012704, P30GM133893
• WS
  Washington State University
• WT
  Wellcome Trust

  Awards: 223619/Z/21/Z, 221708/Z/20/Z
• OP
  Open Philanthropy Project
• EC
  European Commission

  Awards: 899987, 850974
• NN
  Novo Nordisk
• NI
  National Institutes of Health

  Awards: P30GM133893, 17-ID-1
• OO
  Office of Science

  Awards: SC0012704, KP1607011, DE-SC0012704
• NI
  National Institute of General Medical Sciences

  Awards: P30GM133893, 17-ID-1
• BA
  Biological and Environmental Research

  Awards: DE-SC0012704, KP1607011