The Middle Eastern Cousin: Comparative Venomics of Daboia palaestinae and Daboia russelii

Abstract

Among the medically most important snakes in the world, the species belonging to the genus Daboia have been attributed to the highest number of human envenomings, deaths and disabilities. Given their significant clinical relevance, the venoms of Russell's vipers (D. russelii and D. siamensis) have been the primary focus of research. In contrast, the composition, activity, ecology and evolution of venom of its congener, the Palestine viper (D. palaestinae), have remained largely understudied. Therefore, to unravel the factors responsible for the enhanced medical relevance of D. russelii in comparison to D. palaestinae, we comparatively evaluated their venom proteomes, biochemical activities, and mortality and morbidity inflicting potentials. Furthermore, the synthesis and regulation of venom in snakes have also remained underinvestigated, and the relative contribution of each venom gland remains unclear. We address this knowledge gap by sequencing the tissue transcriptomes of both venom glands of D. palaestinae, and comparatively evaluating their contribution to the secreted venom concoction. Our findings highlight the disparity in the venom composition, function and toxicities of the two Daboia species. We also show that toxin production is not partitioned between the two venom glands of D. palaestinae.

Keywords: Daboia palaestinae; Daboia russelii; preclinical assessment; snake venoms; transcriptomes; venomics.

Figure 1

Sampling locations of D. palaestinae (Israel) and D. russelii (India), along with their representative photographs, are shown. Panel (A) depicts the comparative SDS-PAGE profiles of D. palaestinae (DP) and D. russelii (DR) venoms (M: protein marker), while their respective RP-HPLC profiles are shown in panels (B,C).

Figure 2

Venom proteome and venom gland transcriptomes of D. palaestinae. Here, the doughnut charts indicate the relative abundance of various toxins in the (A) venom profile of D. palaestinae and (B) tissue transcriptomes of the left and right venom glands of this species.

Figure 3

Biochemical activities of Daboia venoms. This figure depicts (A) PLA₂, (B) LAAO, and (C) proteolytic (with and without SVMP and SVSP inhibitors) activities of Daboia venoms. Here, the standard deviation is represented as error bars (PC: positive control; DR: D. russelii; DP: D. palaestinae). The statistical significance is represented as follows: p < 0.01 and 0.0001 are indicated as ** and ****, respectively. ns indicates statistical insignificance.

Figure 4

Preclinical assessment of Daboia venoms. This figure depicts the (A) LD₅₀ of D. russelii and D. palaestinae venoms, MHDs of (B) D. palaestinae and (C) D. russelii venom, and the (D) MND of D. russelii venom.

Figure 5

Microscopic observations of mouse kidney sections. This figure shows hematoxylin-eosin and Masson’s trichrome stained kidney sections of the control mice (A,D), and D. russelii (B,E) and (D). palaestinae (C,F) venom-injected mice. A scale bar of 20 μm is shown, along with green, yellow and black arrows that indicate glomerular capsular space shrinkage, tubular injury and cellular debris, respectively.