Chemical synthesis and pharmacological characterization of four alpha neurotoxins isolated from the venom of Micrurus corallinus (coral snake).

Abstract

The coral snakes are the only elapids found in the New World, being Micrurus the most diverse and abundant genus across Americas. In Brazil, the envenomation accidents reported are mainly due to M. corallinus and M. frontalis, which occupy highly populated areas in central, south and southeast of the country. Despite the fact that bites are rare, accidents caused by these snakes are considered dangerous, due to the high toxicity of the venom that contains a lethal combination of pre- and post-synaptic neurotoxins. The major symptoms of envenomation by coral snakes are caused by progressive neuromuscular blockade which can lead to respiratory paralysis and death. Over the past 22 years, researchers from the Butantan Institute, led by Dr. Paulo Lee Ho, have identified five of the most abundant neurotoxins from M. corallinus venom: four ±-neurotoxins (3FTx), which are presumed to have a post-synaptic action, and a phospholipase A2, presumed to be responsible for the presynaptic toxicity of the venom.The main proposal of this work is to pharmacologically and biochemically characterize the mode of action of the four most abundant three-finger toxins from the venom of M. corallinus coral snake. As a first question, we would like to know the toxicity levels of these toxins and their contribution to the overall lethality of the venom. Next, we would like to verify the mode of action of these toxins on nicotinic acetylcholine receptors (nAChR). Finally, we intend to verify if antibodies generated against these neurotoxins would be sufficient to neutralize the lethality of the Micrurus corallinus venom and also, if such antibodies present cross-reactivity with components of other elapids. (AU)