Full Neutralization of Centruroidessculpturatus Scorpion Venom by Combining Two Human Antibody Fragments.

Lidia Riaño-Umbarila,Baltazar Becerril,José Alberto Romero-Moreno,Lourival D. Possani,Luis M. Ledezma-Candanoza,Timoteo Olamendi-Portugal

doi:10.3390/toxins13100708

Abstract

A fundamental issue of the characterization of single-chain variable fragments (scFvs), capable of neutralizing scorpion toxins, is their cross-neutralizing ability. This aspect is very important in Mexico because all scorpions dangerous to humans belong to the Centruroides genus, where toxin sequences show high identity. Among toxin-neutralizing antibodies that were generated in a previous study, scFv 10FG2 showed a broad cross-reactivity against several Centruroides toxins, while the one of scFv LR is more limited. Both neutralizing scFvs recognize independent epitopes of the toxins. In the present work, the neutralization capacity of these two scFvs against two medically important toxins of the venom of Centruroides sculpturatus Ewing was evaluated. The results showed that these toxins are recognized by both scFvs with affinities between 1.8 × 10−9 and 6.1 × 10−11 M. For this reason, their ability to neutralize the venom was evaluated in mice, where scFv 10FG2 showed a better protective capacity. A combination of both scFvs at a molar ratio of 1:5:5 (toxins: scFv 10FG2: scFv LR) neutralized the venom without the appearance of any signs of intoxication. These results indicate a complementary activity of these two scFvs during venom neutralization.

Highlights

Introduction iationsCentruroides sculpturatus Ewing scorpion (C. sculpturatus) is one of the toxic species ofNorth America that is distributed in the United States (Arizona, California, Nevada, New Mexico, and Utah) and along the border with the Mexican state of Sonora [1]
LR for some toxins, it was decided to evaluate their neutralizing capacity of other scorpion venoms of the Centruroides genus
The sequences of the main toxic components of of C. sculpturatus venom were aligned with other toxins that are neutralized by these

Summary

Introduction

Centruroides sculpturatus Ewing scorpion (C. sculpturatus) is one of the toxic species of. North America that is distributed in the United States (Arizona, California (southeastern border), Nevada (southern border), New Mexico (western border), and Utah) and along the border with the Mexican state of Sonora [1]. It is the least toxic of the species evaluated so far, with an LD50 of 22.7 μg/20 g of mouse [4]. A recent characterization of this venom showed the presence of two main toxic components named CsEM1a and CsEd with abundances of 8% and. Like other toxins from Mexican scorpions, these two modify the activity of mammalian sodium channels [6,7,8]. There is an antivenom of equine origin [9], the alternative of producing an antivenom based on antibody fragments of Licensee MDPI, Basel, Switzerland

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Conclusion