Geographic heterogeneity of Deinagkistrodon acutus venom: A multi-regional study of toxicity, proteomics, and antivenom efficacy.

Snakebite envenomation caused by Deinagkistrodon acutus is a severe public health problem. Growing evidence indicates that snake venom exhibits obvious intraspecific geographic variation, which directly affects toxicity, organ damage, and antivenom efficacy. However, systematic studies on the geographic heterogeneity of D. acutus venom remain insufficient. In this study, we collected venoms from different geographical populations of D. acutus in China and performed a comprehensive analysis of lethality, plasma biochemistry, coagulation function, histopathology, proteomics, and antivenom neutralization. The results showed that venoms from different regions exhibited significant differences in LD50. Histopathological examination revealed that the spleen and lung were the main target organs, and the severity of multi-organ injury varied greatly among regions. Proteomic analysis revealed that all venoms shared a core protein set, whereas the composition and abundance of phospholipase A2 and snake venom metalloproteinase exhibited marked geographic diversity, and these compositional differences were closely correlated with variations in venom potency. Importantly, commercial antivenom showed effective neutralization against venoms from eastern regions but significantly reduced protective efficacy against southern and western populations. In conclusion, D. acutus venoms from different geographical origins present remarkable heterogeneity in toxicity, organ pathogenicity, toxin composition, and antivenom reactivity. This study provides key evidence for understanding venom geographic variation and offers an important theoretical basis for optimizing clinical treatment and developing region-adapted antivenoms.