Poneratoxin: structure and function of the major active component from the venom of the bullet ant, the world’s most painful stinging insect

Paraponera clavata, often called the “bullet ant” because stings by this species are sometimes described as feeling like being hit by a bullet, is a large Neotropical ant species that is common in the Atlantic secondary and primary rain forests from Nicaragua through Amazonas. The sting produces characteristic waves of excruciating pain lasting 12+ hours and an uncontrollable urge to shake the afflicted body part. These properties have led to the use of stings by Paraponera as a test for manhood in puberty rites in parts of the Amazon basin. Additionally, the venom is exceedingly lethal to mammals, making this one of the most dangerous, and legitimately respected stinging insects in the world. Until now the venom component(s) responsible for the most profound venom activities has eluded chemical characterization. We characterized and synthesized poneratoxin and its precursor, peptides that are highly lethal, that induce symptoms like a native sting when injected intradermally, and are modifiers of voltage-gated sodium channels in the nervous system. The structure and activity of poneratoxin and its potential for basic understanding and potential beneficial use will be presented.