Venom proteomics and antivenom neutralization for the Chinese eastern Russell’s viper, Daboia siamensis from Guangxi and Taiwan

Abstract

The eastern Russell’s viper (Daboia siamensis) causes primarily hemotoxic envenomation. Applying shotgun proteomic approach, the present study unveiled the protein complexity and geographical variation of eastern D. siamensis venoms originated from Guangxi and Taiwan. The snake venoms from the two geographical locales shared comparable expression of major proteins notwithstanding variability in their toxin proteoforms. More than 90% of total venom proteins belong to the toxin families of Kunitz-type serine protease inhibitor, phospholipase A2, C-type lectin/lectin-like protein, serine protease and metalloproteinase. Daboia siamensis Monovalent Antivenom produced in Taiwan (DsMAV-Taiwan) was immunoreactive toward the Guangxi D. siamensis venom, and effectively neutralized the venom lethality at a potency of 1.41 mg venom per ml antivenom. This was corroborated by the antivenom effective neutralization against the venom procoagulant (ED = 0.044 ± 0.002 µl, 2.03 ± 0.12 mg/ml) and hemorrhagic (ED50 = 0.871 ± 0.159 µl, 7.85 ± 3.70 mg/ml) effects. The hetero-specific Chinese pit viper antivenoms i.e. Deinagkistrodon acutus Monovalent Antivenom and Gloydius brevicaudus Monovalent Antivenom showed negligible immunoreactivity and poor neutralization against the Guangxi D. siamensis venom. The findings suggest the need for improving treatment of D. siamensis envenomation in the region through the production and the use of appropriate antivenom.

Evaluation of the geographical utility of Eastern Russell’s viper (Daboia siamensis) antivenom from Thailand and an assessment of its protective effects against venom-induced nephrotoxicity

“…The avidity ELISA was more discriminatory, with the strength of antibody-venom protein binding greatest for both antivenoms against the Thai D. siamensis venom (Figure 3). These results are in line with a previous study, which showed that the Thai DSAV antivenom exhibits immunoreactivity to D. siamensis venoms from Taiwan and Guanxi, South China, but to a lesser extent than the binding observed with Chinese monovalent antivenom [17].…”

“…However, the treatment of systemic envenoming caused by D. siamensis has long been problematic in many Asian countries, due to challenges related to the access of antivenom and the dosing regimen used to effect cure. For example, in southern parts of mainland China, where envenoming by D. siamensis poses a substantial health problem, access to monovalent antivenoms is very limited, which has resulted in the use of non-specific or species-inappropriate antivenoms, leading to reports of treatment failures and mortality [17]. Herein, we examined the effectiveness of the Thai monovalent D. siamensis (DSAV) and Hemato Polyvalent (HPAV) antivenoms against three different geographical variants of D. siamensis using in vitro biochemical and immunological assays.…”

“…Other toxin families (e.g. L-amino acid oxidases, serine proteases and C-type-lectin-like proteins [9]) likely contribute to pathology following envenoming by Russell’s vipers, and together with the PLA 2 and SVMPs, these toxin families comprise >90% of all of the toxins found in the venom proteome [17]. In terms of specific toxins, prior studies have demonstrated that the SVMP RVV-X is a potent activator of Factor X [18], and thus contributes to the depletion of coagulation factors (notably fibrinogen), resulting in a syndrome similar to disseminated intravascular coagulation (DIC) termed venom-induced consumption coagulopathy (VICC) [19].…”

“…Previous studies have reported a degree of cross-neutralizing effect between the HPAV and DSAV antivenoms from Thailand against the toxicity of D. siamensis venoms from different geographical localities, i.e . Myanmar and Taiwan, in preclinical studies and ELISA binding experiments, respectively, although their efficacy was seemingly lower than that of local antivenoms made using venom from those localities [17, 23]. However, despite the Myanmar Pharmaceutical Factory producing 46,000 vials of Russell’s viper antivenom annually, this volume is seemingly insufficient to treat the total burden of D. siamensis envenomings in country [24].…”

Proteomics and antivenom immunoprofiling of Russell’s viper (Daboia siamensis) venoms from Thailand and Indonesia

“…The recent venomic study of Eastern Russell's viper from Taiwan and China revealed geographical venom variation that supports the clinical observation of envenoming effects [17,18]. In Southeast Asia, the proteomics of D. siamensis venom from Myanmar was previously reported [19]; however, an indepth venom proteome that details the protein subtypes and expression level for D. siamensis originating from Southeast Asia remains to be elucidated.…”