A sharp eye on the venom of one of Asia's most dangerous pitvipers
Avella, Ignazio
Animal Venomics Lab
Fraunhofer Institute for Molecular Biology and Applied Ecology (IME)
Ohlebergsweg 12, 35392
Giessen, Germany
Institute for Insect Biotechnology, Justus Liebig University Giessen
Heinrich-Buff-Ring 26–32, 35392
Giessen, Germany
LOEWE-Centre for Translational Biodiversity Genomics (LOEWE-TBG)
Natural Product Genomics
Senckenberganlage 25, 60325
Frankfurt am Main, Germany
The Sharp-nosed Viper (Deinagkistrodon acutus) is one of the snakes of highest medical importance in the Asian continent. The venom of this species has been investigated in several studies using different modern venomics techniques, but this wealth of knowledge has yet to be fully utilised, and a comprehensive understanding of its composition and function remains lacking. By combining proteogenomics with extensive bioactivity profiling, we present the first genome-level catalogue of D. acutus venom proteins and their exochemistry. Our analysis identified a relatively simple venom containing 45 components from 20 distinct protein families. Relative toxin abundances indicate that C-type lectin and C-type lectin-related protein (CTL), snake venom metalloproteinase (svMP), snake venom serine protease (svSP), and phospholipase A2 (PLA2) constitute 90% of the venom proteome. Bioassays targeting key aspects of viperid envenomation revealed considerable concentration-dependent cytotoxicity, particularly in kidney and lung cells, along with potent protease and PLA2 activity. Factor Xa and thrombin activities were minor, and no plasmin activity was observed. Effects on haemolysis, intracellular calcium (Ca2+) release, and nitric oxide (NO) synthesis were negligible. By providing the first holistic genome-based picture of the toxin arsenal of D. acutus, and predicting the molecular and functional basis of its life-threatening effects, our analysis opens novel avenues for treating envenomation by this highly dangerous pitviper.