Abstract
BACKGROUND: Russell's viper (Daboia russelii) is the clinically most important snake species in the world. Considerable variation has been documented in D. russelii venoms across the Indian subcontinent, which can drive the diverse envenomation profiles in snakebite victims. Therefore, understanding the role of ecological and environmental factors influencing the compositional and functional variation can provide critical insights into the complex evolutionary adaptations of this species and pave the way for the development of targeted therapies. METHODS: We examined the influence of bioclimatic factors on D. russelii venom functions by analysing 115 samples sourced from various locations across India. The enzymatic activities of major toxins, such as proteases and phospholipases, were estimated to capture the functional variation in these venoms. Multiple regression models were developed to evaluate the relationship between venom variability and the historical climate data, specifically temperature and precipitation. Furthermore, predictive models were employed to map venom phenotypes across the distribution range of D. russelii. FINDINGS: Our findings reveal a collective influence of various temperature and precipitation parameters that partly explain the variability in enzymatic activities of D. russelii venom. Our models effectively captured regional differences in venom composition and linked climatic conditions with functional variations. CONCLUSION: This study highlights the significant role of abiotic factors in shaping the venom profiles of Russell's vipers across India. The predictive venom phenotype maps developed from our models can guide the deployment of targeted therapies and treatment protocols across the biogeographically diverse Indian subcontinent and improve clinical treatment outcomes of D. russelii envenoming. This research enhances our understanding of venom phenotype evolution and has practical implications for improving snakebite management.