Molecular Recognition and Immunopharmacological Implications of Serratiopeptidase Targeting Snake Venom Bradykinin-Potentiating Peptides

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  Molecular Recognition and Immunopharmacological Implications of Serratiopeptidase Targeting Snake Venom Bradykinin-Potentiating Peptides Abstract Purpose Bradykinin-potentiating peptides (BPPs), found in snake venom, are known to modulate cardiovascular functions, but their susceptibility to enzymatic degradation remains poorly understood. Methods Models were generated using AlphaFold-Colab for five small BPPs (< 9 amino acids) that did not have experimentally solved structures, and those BPPs which had reliable predictions of structure (pLDDT > 80) were used for docking studies. Protein-peptide docking experiments were done using HADDOCK for studying the interaction between wild-type (WT) and mutant serratiopeptidase with BPPs. After selecting the best complex, simulation of the complex was done using molecular dynamics (MD) simulations for 100 ns and binding energy determination using MM/PBSA analysis. For checking the mechanical stability of the protein-peptide complexes...

Identification of a common epitope in knottins and phospholipases D present in Loxosceles sp venom by a monoclonal antibody

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Identification of a common epitope in knottins and phospholipases D present in Loxosceles sp venom by a monoclonal antibody

Abstract

In the Americas and specially in Brazil, the Loxosceles intermedia, Loxosceles gaucho and Loxosceles laeta are the three most medically relevant brown spider species, and whose bites can lead to the condition known as loxoscelism. Here, we report the development of a tool capable of identifying a common epitope amongst Loxosceles sp. venom's toxins. A murine monoclonal antibody (LmAb12) and its recombinant fragments (scFv12P and diabody12P) have been produced and characterized. This antibody and its recombinant constructs were able to recognize proteins of Loxosceles spider venoms with specificity. The scFv12P variant was also able to detect low concentrations of Loxosceles venom in a competitive ELISA assay, displaying potential as a venom identification tool. The primary antigenic target of LmAb12 is a knottin, a venom neurotoxin, that has a shared identity of 100 % between the L. intermedia and L. gaucho species and high similarity to L. laeta. Furthermore, we observed LmAb12 was able to partially inhibit in vitro hemolysis, a cellular event typically induced by the Loxosceles sp. venoms. Such behavior might be due to LmAb12 cross-reactivity between the antigenic target of LmAb12 and the venom's dermonecrotic toxins, the PLDs, or even the existence of synergism between these two toxins.

Camila Alves-Mondini, Martina Beltramino, Isabella Gizzi Jiacomini, Sabrina Karim-Silva, Nicolle dos Santos Antunes, Juliana de Moura, Nicolas Aubrey, Philippe Billiald, Ricardo Andrez Machado-de-Ávila, Larissa M. Alvarenga, Alessandra Becker-Finco, Identification of a common epitope in knottins and phospholipases D present in Loxosceles sp venom by a monoclonal antibody, International Journal of Biological Macromolecules, Volume 246, 2023, 125588, ISSN 0141-8130, https://doi.org/10.1016/j.ijbiomac.2023.125588.

(https://www.sciencedirect.com/science/article/pii/S0141813023024820)