Haemostasis disorders caused by envenomation by Cerastes cerastes and Macrovipera mauritanica vipers.

Viper venoms are a real source of proteolytic enzymes causing clotting, bleeding, edema, necrosis, hemorrhage, pain at the bite site and systemic changes. This study was conducted to evaluate the changes induced in hematological and haemostatic parameters in rabbits after 1, 3, 6 and 24 h post-venom of subcutaneously administration of a sublethal dose of Cerastes cerastes and Macrovipera mauritanica venoms. Our results indicated that most hematological and haemostatic parameters showed significant changes 3 and 6 h after envenomation. The hemoglobin, hematocrit, red blood cells, platelets and prothrombin time were reduced significantly 3 h after envenomation. A very significant increase in the levels of white blood cells, lymphocytes, monocytes, activated thromboplastin time and fibrinogen were recorded 6 h following envenomation. However, no significant difference was found for the mean corpuscular volume, corpuscular hemoglobin content and mean corpuscular hemoglobin concentration throughout the whole duration of the experiment. These results suggest that severe hematological and haemostatic changes may be initiated during the early stages of envenomation leading to local and systemic hemorrhages and coagulopathies which are the main cause of death in case of vipers envenomation.

Venomics and antivenomics profiles of North African Cerastes cerastes and C. vipera populations reveals a potentially important therapeutic weakness.

We report the proteomic analysis of the venom of the medically relevant snake, Cerastes cerastes, from Morocco, and the immunoreactivity profile of an experimental monospecific (CcMo_AV against Moroccan C. cerastes venom) and a commercial (Gamma-VIP against Tunisian C. cerastes and M. lebetina venoms) F(ab')(2) antivenoms towards geographic variants of C. cerastes and C. vipera venoms. The venom of C. cerastes is a low-complexity proteome composed of 25-30 toxins belonging to 6 protein families, mainly targetting the hemostatic system. This toxin arsenal explains the clinical picture observed in C. cerastes envenomings. Despite geographic compositional variation, the monospecific CcMo_AV and the Gamma-VIP divalent antivenom produced at Institut Pasteur de Tunis, showed similar immunocapturing capability towards Moroccan, Tunisian, and Egyptian C. cerastes venom proteins. Proteins partially escaping immunorecognition were all identified as PLA(2) molecules. Antivenomic analysis showed low degree of cross-reactivity of Moroccan CcMo_AV and Tunisian Gamma-VIP antivenoms towards C. vipera venom toxins. This study indicates that a more complete therapeutic cover could be achieved by including C. vipera venom in the formulation of venom immunization mixtures, thereby generating a pan-Cerastes antivenom.

Snake venomics of Macrovipera mauritanica from Morocco, and assessment of the para-specific immunoreactivity of an experimental monospecific and a commercial antivenoms.

Proteomic analysis of the venom of the medically relevant snake Macrovipera mauritanica from Morocco revealed a complex proteome composed of at least 45 toxins from 9 protein families targeting the hemostatic system of the prey or victim. The toxin profile of Moroccan M. mauritanica displays great similarity, but also worth noting departures, with the previously reported venom proteome of M. lebetina from Tunisia. Despite fine compositional differences between these Macrovipera taxa, their overall venom phenotypes explain the clinical picture observed in M. mauritanica and M. lebetina envenomings. However, M. mauritanica venom also contains significant amounts of orphan molecules whose presence in the venom seems to be difficult to rationalize in the context of a predator-prey arms race. The paraspecific immunoreactivity of an experimental monospecific (M. mauritanica) antivenom and a commercial bivalent antivenom, anti-C. cerastes and anti-M. lebetina, against the venoms of Moroccan M. mauritanica and Tunisian M. lebetina, was also investigated through an affinity chromatography-based antivenomics approach. Both antivenoms very efficiently immunodepleted homologous venom toxins and displayed a high degree of paraspecificity, suggesting the clinical utility of the two antivenoms for treating bites of both M. mauritanica or M. lebetina.