Scorpion Venom Peptides: Novel Therapeutic Approaches for Inflammatory and Hepatic Disorders

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  Scorpion Venom Peptides: Novel Therapeutic Approaches for Inflammatory and Hepatic Disorders Abstract Chronic hepatic disorders, such as metabolic dysfunction associated steatohepatitis (MASH), alcohol associated liver disease (ALD), and viral hepatitis (Hepatitis B Virus [HBV]/Hepatitis C Virus [HCV]), are primarily driven by persistent immune-mediated inflammation and hepatic stellate cell activation leading to fibrosis, yet conventional therapies lack tissue and molecular specificity. Scorpion venom peptides, refined through evolutionary selection, provide highly potent, target specific scaffolds capable of modulating intrahepatic inflammatory networks. Recent in vivo preclinical studies indicate that voltage gated potassium (Kv1.3) channel blocking peptides, such as BmKK2, significantly reduce macrophage activation and inhibit downstream cytokine production, effectively ameliorating diet-induced steatohepatitis and tissue scarring in murine models. Engineered hepatotropic ca...

Venom characterization and structural insights into phospholipase D isoforms from the spider Loxosceles aff. variegata

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Venom characterization and structural insights into phospholipase D isoforms from the spider Loxosceles aff. variegata

Abstract

Brown spider envenomation (loxoscelism) represents a significant public health concern in South America, yet most studies focus on a few medically recognized species. Here, we provide the first molecular and functional characterization of the venom gland extract from Loxosceles aff. variegata (LafvVGE), a brown spider collected in synanthropic habitats in Ituiutaba, Minas Gerais, Brazil. SDS-PAGE and immunoblot analyses revealed prominent protein bands consistent with phospholipase D (PLD) toxins, the main agents of loxoscelism symptoms. ELISA assays demonstrated that LafvVGE is effectively recognized by Brazilian therapeutic antivenoms, indicating immunological cross-reactivity. Enzymatic assays confirmed sphingomyelinase and collagenase/gelatinase activities comparable to those of Loxosceles gaucho (a species of acknowledged medical relevance), although LafvVGE from female individuals showed higher activities than male derived pools under our experimental conditions. Neutralization assays showed complete inhibition of sphingomyelinase activity but only partial inhibition of gelatinase activity by the anti-loxoscelic antivenom, highlighting differential susceptibility of venom components to antivenom-mediated neutralization under in vitro conditions. Molecular analysis of venom gland transcripts identified eight distinct PLD isoforms (LafvPLD1–8), all containing conserved catalytic and metal-binding residues characteristic of class II Loxosceles PLDs. Structural modeling revealed isoform-specific variations in the aromatic cage motif and electrostatic surface, suggesting potential effects on membrane interactions and substrate specificity. Collectively, these findings place L. aff. variegata within the biochemical and structural spectrum of medically relevant Loxosceles species, expanding comparative knowledge of PLD diversity and function. While clinical relevance remains to be established in vivo, this study underscores the value of integrating biochemical, immunological, and structural analyses to identify emerging venom phenotypes with potential implications for surveillance and antivenom coverage.
Silva-Araújo, A. L., Silva-Magalhães, R., Peres-Damásio, P., Pereira, E. H. T., De Oliveira Souza, R., Varela, L. S. D. R. N., Ribeiro Tomé, L. M., Campos de Melo Iani, F., Silveira, A. L., Borges, M. H., Medina-Santos, R., Chavez-Olórtegui, C., Vasconcelos Diniz, M. R., Bittencourt Paiva, A. L., & Guerra-Duarte, C. (2026). Venom characterization and structural insights into phospholipase D isoforms from the spider Loxosceles aff. Variegata. Toxicon, 109129. https://doi.org/10.1016/j.toxicon.2026.109129