The hills are alive with the sound of venom: Clinical implications of intraspecific variations in Factor Va mediated activations of Factor VII and Factor X in Swiss populations of Vipera aspis (Asp Viper)

 

The hills are alive with the sound of venom: Clinical implications of intraspecific variations in Factor Va mediated activations of Factor VII and Factor X in Swiss populations of Vipera aspis (Asp Viper)

ABSTRACT

This study investigated the individual variation in the procoagulant toxicity of Vipera aspis venoms collected from multiple Swiss localities, in addition to the neutralisation capacity of three currently available antivenoms. Functional coagulation assays revealed quantifiable geographic differences in venom potency and clotting kinetics. Mechanistic analyses demonstrated that V. aspis venoms exert their procoagulant effects primarily through Factor Va-dependent action of the coagulation cascade, leading to accelerated thrombin generation and clot formation. These findings highlight the complexity of venom-host interactions, showing that Factor Va acts as a multifactorial cofactor that mediates both Factor X and Factor VII activation and varies between individual specimens. From a clinical perspective, this toxicological variability underscores the challenges or relying on a single antivenom for effective treatment across the vast range of a single species. Understanding the molecular basis of these pathophysiological variations through proteomic or transcriptomic profiling will be critical for developing antivenoms with improved neutralising efficacy. Beyond its clinical toxicology relevance, this work provides novel insight into the ecological and evolutionary forces shaping venom diversity in medically important species and identifies procoagulant enzymes from V. aspis venom as promising lead candidates for therapeutic development.

Kempson, K., Champagne, P. S., Seneci, L., Jones, L., Ursenbacher, S., Dubey, S., Joudrier, N., Aldridge, M., Soria, R., & Fry, B. G. (2026). The hills are alive with the sound of venom: Clinical implications of intraspecific variations in Factor Va mediated activations of Factor VII and Factor X in Swiss populations of Vipera aspis (Asp Viper). Biochimie. https://doi.org/10.1016/j.biochi.2026.02.009