A Genus-Wide Bioactivity Analysis of (Viperinae: Viperidae) Viper Venoms Reveals Widespread Variation in Haemotoxic Properties.

The snake genus (Viperidae: Viperinae; Oppel, 1811) contains five species: , , and , found in Afro-Arabia, and the Russell's vipers and , found in Asia. Russell's vipers are responsible for a major proportion of the medically important snakebites that occur in the regions they inhabit, and their venoms are notorious for their coagulopathic effects. While widely documented, the extent of venom variation within the Russell's vipers is poorly characterised, as is the venom activity of other species within the genus. In this study we investigated variation in the haemotoxic activity of using twelve venoms from all five species, including multiple variants of , and . We tested the venoms on human plasma using thromboelastography, dose-response coagulometry analyses, and calibrated automated thrombography, and on human fibrinogen by thromboelastography and fibrinogen gels. We assessed activation of blood factors X and prothrombin by the venoms using fluorometry. Variation in venom activity was evident in all experiments. The Asian species and and the African species possessed procoagulant venom, while and were net-anticoagulant. Of the Russell's vipers, the venom of from Myanmar was most toxic and of Sri Lanka the least. Activation of both factor X and prothrombin was evident by all venoms, though at differential levels. Fibrinogenolytic activity varied extensively throughout the genus and followed no phylogenetic trends. This venom variability underpins one of the many challenges facing treatment of snakebite envenoming. Comprehensive analyses of available antivenoms in neutralising these variable venom activities are therefore of utmost importance.