Targeting snake venom metalloproteinases: structural diversity, molecular pathogenesis and therapeutic interventions

Posted by
  Targeting snake venom metalloproteinases: structural diversity, molecular pathogenesis and therapeutic interventions Abstract Snake venom Metalloproteinases (SVMPs) are Zn²⁺-dependent endopeptidases categorised under metzincin superfamily and are predominantly found in venom of the “ Viperidae ” family snakes. They are key mediators of venom-induced pathology with associated tissue damage including haemorrhage and oedema. SVMPs are classified as P-I, P-II, and P-III depending on the domains, each differing in structural complexity and organization. Further, the conserved HEXXHXXGXXH catalytic motif organizes a Zn 2+ ion, essential for the breakdown of peptide bonds and proteins. Given the limitations of conventional antivenom therapy, increasing attention has been directed toward targeted approaches for SVMPs neutralization, including plant-derived phytocompounds, synthetic and repurposed small-molecule inhibitors, recombinant monoclonal antibodies, and camelid-derived nanobodi...

Thromboinflammatory complications of Bothrops snakebite envenoming: the case of B. lanceolatus endemic to the Caribbean Island of Martinique

Posted by

Photo 364017349, (c) Vincent Rufray, some rights reserved (CC BY-NC), uploaded by Vincent Rufray (iNaturalist)

Thromboinflammatory complications of Bothrops snakebite envenoming: the case of B. lanceolatus endemic to the Caribbean Island of Martinique

Abstract

Snakebite envenoming remains a predominant neglected disease in tropical and subtropical regions, with high rates of morbidity and mortality worldwide. Bothrops snakebite envenoming. is characterized by severe injuries at the site of venom injection, which include tissue necrosis, hemorrhage, blistering, and edema. Haemotoxicity is typically attributed to the strong procoagulant state induced by the majority Bothrops venoms leading to coagulation factor consumption and incoagulable blood. Concomitantly with this procoagulant state, a complex host response develops in the affected tissues, accompanied by the recruitment of inflammatory and immunocompetent cells, along with the activation of resident cells, and the synthesis of a plethora of pro-inflammatory mediators and damage-associated molecular patterns from injured tissue. An increasing body of evidence suggests that this intricate response is, in fact, related to the well-documented immunothrombosis and thromboinflammation integrated features. Of note, thrombotic complications are extremely rare in Bothrops snakebite envenoming. However, in the case of Bothrops lanceolatus and B. caribbaeus, which are respectively endemic to Martinique and St. Lucia, the absence of overt consumption coagulopathy due to their weak procoagulant effects may be related to the thrombotic effects, as clotting factors are present in the bloodstream by the time the thrombogenic and inflammatory mechanisms are operating in blood vessels. Prior to the era of immunotherapy, B. lanceolatus envenoming was associated with thrombotic complications in 25% of cases and was fatal in approximately 10% of cases. This review examines the potential role of thromboinflammation as a mechanism of thrombotic accidents in B. lanceolatus snakebite envenoming.

Rapon, C., Florentin, J., Radouani, F., Jalta, P., Negrello, F., Gueye, P., Neviere, R., & Resiere, D. (2025). Thromboinflammatory complications of Bothrops snakebite envenoming: The case of B. Lanceolatus endemic to the Caribbean Island of Martinique. Frontiers in Immunology, 16, 1625165. https://doi.org/10.3389/fimmu.2025.1625165