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In this communication the isolation, chemical and physiological characterization of three new toxins from the scorpion Centruroides baergi are reported. Their immunoreactive properties with scFvs generated in our group are described. The three new peptides, named Cb1, Cb2 and Cb3 affect voltage-dependent Na+ channels in a differential manner. These characteristics, explain the toxicity of this venom. Molecular interactions in real-time among these toxins and the best recombinant antibodies generated in our group, revealed that one of them was able to neutralize the main toxin of this venom (Cb1). These results represent an important advance for the neutralization of this venom and serve as the basis for generating new scFvs that will allow the neutralization of similar toxins from other venoms that have no yet been neutralized.
Ilse V. Gómez-Ramírez; Lidia Riaño-Umbarila; Timoteo Olamendi-Portugal; Rita Restano-Cassulini; Lourival D. Possani; Baltazar Becerril. Biochemical, electrophysiological and immunological characterization of the venom from Centruroides baergi, a new scorpion species of medical importance in Mexico. Toxicon 2020, 184, 10 -18.
AMA StyleIlse V. Gómez-Ramírez, Lidia Riaño-Umbarila, Timoteo Olamendi-Portugal, Rita Restano-Cassulini, Lourival D. Possani, Baltazar Becerril. Biochemical, electrophysiological and immunological characterization of the venom from Centruroides baergi, a new scorpion species of medical importance in Mexico. Toxicon. 2020; 184 ():10-18.
Chicago/Turabian StyleIlse V. Gómez-Ramírez; Lidia Riaño-Umbarila; Timoteo Olamendi-Portugal; Rita Restano-Cassulini; Lourival D. Possani; Baltazar Becerril. 2020. "Biochemical, electrophysiological and immunological characterization of the venom from Centruroides baergi, a new scorpion species of medical importance in Mexico." Toxicon 184, no. : 10-18.
The recombinant antibody fragments generated against the toxic components of scorpion venoms are considered a promising alternative for obtaining new antivenoms for therapy. Using directed evolution and site-directed mutagenesis, it was possible to generate a human single-chain antibody fragment with a broad cross-reactivity that retained recognition for its original antigen. This variant is the first antibody fragment that neutralizes the effect of an estimated 13 neurotoxins present in the venom of nine species of Mexican scorpions. This single antibody fragment showed the properties of a polyvalent antivenom. These results represent a significant advance in the development of new antivenoms against scorpion stings, since the number of components would be minimized due to their broad cross-neutralization capacity, while at the same time bypassing animal immunization.
Lidia Riaño-Umbarila; Ilse V. Gómez-Ramírez; Luis M. Ledezma-Candanoza; Timoteo Olamendi-Portugal; Everardo Remi Rodríguez-Rodríguez; Guillermo Fernández-Taboada; Lourival D. Possani; Baltazar Becerril. Generation of a Broadly Cross-Neutralizing Antibody Fragment against Several Mexican Scorpion Venoms. Toxins 2019, 11, 32 .
AMA StyleLidia Riaño-Umbarila, Ilse V. Gómez-Ramírez, Luis M. Ledezma-Candanoza, Timoteo Olamendi-Portugal, Everardo Remi Rodríguez-Rodríguez, Guillermo Fernández-Taboada, Lourival D. Possani, Baltazar Becerril. Generation of a Broadly Cross-Neutralizing Antibody Fragment against Several Mexican Scorpion Venoms. Toxins. 2019; 11 (1):32.
Chicago/Turabian StyleLidia Riaño-Umbarila; Ilse V. Gómez-Ramírez; Luis M. Ledezma-Candanoza; Timoteo Olamendi-Portugal; Everardo Remi Rodríguez-Rodríguez; Guillermo Fernández-Taboada; Lourival D. Possani; Baltazar Becerril. 2019. "Generation of a Broadly Cross-Neutralizing Antibody Fragment against Several Mexican Scorpion Venoms." Toxins 11, no. 1: 32.
The increment in the number of scorpion envenoming cases in Mexico is mainly associated to the rapid growth of the urban areas, and consequently, to the invasion of natural habitats of these arachnids. On the other hand, there is a great diversity of scorpion species, so it is indispensable to identify those of medical importance, which we now know are many more than the 7-8 previously reported as dangerous to humans. Because different LD50 values have been reported for the venom of the same species, probably due to variations in the experimental conditions used, in this work we determined the LD50 values for the venoms of 13 different species of scorpions using simple but systematic procedures. This information constitutes a referent on the level of toxicity of medically important scorpion species from Mexico and establishes the bases for a more comprehensive assessment of the neutralizing capacity of current and developing antivenoms.
Lidia Riaño-Umbarila; Everardo R. Rodríguez-Rodríguez; Carlos E. Santibañez-López; Leopoldo Güereca; Selene J. Uribe-Romero; Ilse V. Gómez-Ramírez; Edson N. Cárcamo-Noriega; Lourival D. Possani; Baltazar Becerril. Updating knowledge on new medically important scorpion species in Mexico. Toxicon 2017, 138, 130 -137.
AMA StyleLidia Riaño-Umbarila, Everardo R. Rodríguez-Rodríguez, Carlos E. Santibañez-López, Leopoldo Güereca, Selene J. Uribe-Romero, Ilse V. Gómez-Ramírez, Edson N. Cárcamo-Noriega, Lourival D. Possani, Baltazar Becerril. Updating knowledge on new medically important scorpion species in Mexico. Toxicon. 2017; 138 ():130-137.
Chicago/Turabian StyleLidia Riaño-Umbarila; Everardo R. Rodríguez-Rodríguez; Carlos E. Santibañez-López; Leopoldo Güereca; Selene J. Uribe-Romero; Ilse V. Gómez-Ramírez; Edson N. Cárcamo-Noriega; Lourival D. Possani; Baltazar Becerril. 2017. "Updating knowledge on new medically important scorpion species in Mexico." Toxicon 138, no. : 130-137.
New approaches aimed at neutralizing the primary toxic components present in scorpion venoms, represent a promising alternative to the use of antivenoms of equine origin in humans. New potential therapeutics developed by these approaches correspond to neutralizing antibody fragments obtained by selection and maturation processes from libraries of human origin. The high sequence identity shared among scorpion toxins is associated with an important level of cross reactivity exhibited by these antibody fragments. We have exploited the cross reactivity showed by single chain variable antibody fragments (scFvs) of human origin to re-direct the neutralizing capacity toward various other scorpion toxins. As expected, during these evolving processes several variants derived from a parental scFv exhibited the capacity to simultaneously recognize and neutralize different toxins from Centruroides scorpion venoms. A sequence analyses of the cross reacting scFvs revealed that specific mutations are responsible for broadening their neutralizing capacity. In this work, we generated a set of new scFvs that resulted from the combinatorial insertion of these point mutations. These scFvs are potential candidates to be part of a novel recombinant antivenom of human origin that could confer protection against scorpion stings. A remarkable property of one of these new scFvs (ER-5) is its capacity to neutralize at least three different toxins and its complementary capacity to neutralize the whole venom from Centruroides suffusus in combination with a second scFv (LR), which binds to a different epitope shared by Centruroides scorpion toxins.
Everardo Rodríguez; Timoteo Olamendi-Portugal; Hugo Serrano-Posada; Jonathan Noé Arredondo-López; Ilse Gómez-Ramírez; Guillermo Fernández-Taboada; Lourival D. Possani; Gerardo Alfonso Anguiano-Vega; Lidia Riaño-Umbarila; Baltazar Becerril. Broadening the neutralizing capacity of a family of antibody fragments against different toxins from Mexican scorpions. Toxicon 2016, 119, 52 -63.
AMA StyleEverardo Rodríguez, Timoteo Olamendi-Portugal, Hugo Serrano-Posada, Jonathan Noé Arredondo-López, Ilse Gómez-Ramírez, Guillermo Fernández-Taboada, Lourival D. Possani, Gerardo Alfonso Anguiano-Vega, Lidia Riaño-Umbarila, Baltazar Becerril. Broadening the neutralizing capacity of a family of antibody fragments against different toxins from Mexican scorpions. Toxicon. 2016; 119 ():52-63.
Chicago/Turabian StyleEverardo Rodríguez; Timoteo Olamendi-Portugal; Hugo Serrano-Posada; Jonathan Noé Arredondo-López; Ilse Gómez-Ramírez; Guillermo Fernández-Taboada; Lourival D. Possani; Gerardo Alfonso Anguiano-Vega; Lidia Riaño-Umbarila; Baltazar Becerril. 2016. "Broadening the neutralizing capacity of a family of antibody fragments against different toxins from Mexican scorpions." Toxicon 119, no. : 52-63.