State of the art on the development of a recombinant antivenom against Mexican scorpion stings

Abstract

Around 2,750 species of scorpions have been recorded worldwide and classified into 21 families and 208 genera. Of these, the family Buthidae stands out as one of the largest, comprising several genera including the genus Centruroides with 102 recorded species. This genus is home to the largest number of species dangerous to humans as described in Mexico, where there are 55 species of the genus Centruroides, of which more than 24 are of medical importance. Envenoming in humans is caused by the presence of peptides (toxins) in the venom that modify the gating mechanism of Na⁺ voltage dependent ionic channels. Therefore, a rational approach to generate a new antivenom is to obtain neutralizing antibodies against these toxins, whose average abundance in venom is 10%. In this review paper, we document that from the characterization of the lethal venoms of Mexican scorpions, 30 lethal components have been identified, so their neutralization represents an enormous challenge. Thanks to phage display and directed evolution technologies, it has been possible to generate specific antibody fragments against several of these toxins, some of which exhibit broad cross-neutralization. Currently, progress has been made in neutralizing the venoms of 9 species with the use of recombinant antibody fragments, mainly of human origin. One of them has the potential to neutralize approximately 20 toxins.