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...

Loxosceles amazonica Brown Spider venom: Insights into enzymatic activities, immunorecognition, and novel phospholipase D isoforms

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Loxosceles amazonica Brown Spider venom: Insights into enzymatic activities, immunorecognition, and novel phospholipase D isoforms

Abstract

The Loxosceles genus represents one of the main arachnid genera of medical importance in Brazil. Despite the gravity of Loxosceles-related accidents, just a handful of species are deemed medically important and only a few have undergone comprehensive venom characterization. Loxosceles amazonica is a notable example of a potentially dangerous yet understudied Loxosceles species. While there have been limited reports of accidents involving L. amazonica to date, accidents related to Loxosceles are increasing in the North and Northeast regions of Brazil, where L. amazonica has been reported. In this work, we provide a complementary biochemical and immunological characterization of L. amazonica venom, considering its most relevant enzymatic activities and its immunorecognition and neutralization by current therapeutic antivenoms. Additionally, a cDNA library enriched with phospholipase D (PLD) sequences from L. amazonica venom glands was built and subsequently sequenced. The results showed that L. amazonica venom is well immunorecognised by all the tested antibodies. Its venom also displayed proteolytic, hyaluronidase, and sphingomyelinase activities. These activities were at least partially inhibited by available antivenoms. With cDNA sequencing of PLDs, seven new putative isoforms were identified in the venom of L. amazonica. These results contribute to a better knowledge of the venom content and activities of a synanthropic, yet understudied, Loxosceles species. In vivo assays are essential to confirm the medical relevance of L. amazonica, as well as to assess its true toxic potential and elucidate its related pathophysiology.
Silva-Magalhães, R., Silva-Araújo, A. L., Peres-Damásio, P., Teixeira Pereira, E. H., De Oliveira Souza, R., Varela, L. S. D. R. N., Tomé, L. M. R., De Melo Iani, F. C., Silveira, A. L., Borges, M. H., Medina-Santos, R., Chavez-Olórtegui, C., Vasconcelos Diniz, M. R., Paiva, A. L. B., & Guerra-Duarte, C. (2024). Loxosceles amazonica Brown Spider venom: Insights into enzymatic activities, immunorecognition, and novel phospholipase D isoforms. Biochimie, 227, 86-98. https://doi.org/10.1016/j.biochi.2024.06.012