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

J. Venom. Anim. Toxins incl. Trop. Dis

et al. 2021

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Background: The western Russell's viper (Daboia russelii) is widely distributed in South Asia, and geographical venom variation is anticipated among distant populations. Antivenoms used for Russell's viper envenomation are, however, raised typically against snakes from Southern India. The present study investigated and compared the venom proteomes of D. russelii from Sri Lanka (DrSL) and India (DrI), the immunorecognition of Indian VINS Polyvalent Antivenom (VPAV) and its efficacy in neutralizing the venom toxicity. Methods: The venoms of DrSL and DrI were decomplexed with C 18 high-performance liquid chromatography and SDS-polyacrylamide gel electrophoresis under reducing conditions. The proteins fractionated were identified through nano-ESI-liquid chromatography-tandem mass spectrometry (LCMS/MS). The immunological studies were conducted with enzyme-linked immunosorbent assay. The neutralization of the venom procoagulant effect was evaluated in citrated human plasma. The neutralization of the venom lethality was assessed in vivo in mice adopting the WHO protocol. Results: DrSL and DrI venom proteomes showed comparable major protein families, with phospholipases A 2 (PLA 2 ) being the most abundant (> 60% of total venom proteins) and diverse (six protein forms identified). Both venoms were highly procoagulant and lethal (intravenous median lethal dose in mice, LD 50 = 0.24 and 0.32 µg/g, for DrSL and DrI, respectively), while lacking hemorrhagic and anticoagulant activities. VPAV was immunoreactive toward DrSL and DrI venoms, indicating conserved protein antigenicity in the venoms. The high molecular weight venom proteins were, however, more effectively immunorecognized than small ones. VPAV was able to neutralize the coagulopathic and lethal effects of the venoms moderately. Conclusion:Considering that a large amount of venom can be injected by Russell's viper during envenomation, the potency of antivenom can be further improved for optimal neutralization and effective treatment. Region-specific venoms and key toxins may be incorporated into the immunization procedure during antivenom production.

Section: Discussionsupporting

confidence: 92%

Proteomics, toxicity and antivenom neutralization of Sri Lankan and Indian Russell’s viper (Daboia russelii) venoms

Faisal

J. Venom. Anim. Toxins incl. Trop. Dis

et al. 2021

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“…While SVMPs are generally abundantly present in the venom proteomes of Asiatic viperids (for examples see [ 31 , 32 , 33 ]), the abundances of this enzymatic protein family in the Ovophis pit viper venoms studied were relatively low (<20% of total venom proteins). The majority of SVMP detected belong to Class P-III of SVMP, which are high molecular weight proteins containing disintegrin-like and cysteine-rich domains following the ADAM proteinase domain [ 34 , 35 ].…”

Section: Resultsmentioning

confidence: 99%

Snake Venom Proteomics, Immunoreactivity and Toxicity Neutralization Studies for the Asiatic Mountain Pit Vipers, Ovophis convictus, Ovophis tonkinensis, and Hime Habu, Ovophis okinavensis

Palasuberniam

2021

Toxins

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Snakebite envenomation is a serious neglected tropical disease, and its management is often complicated by the diversity of snake venoms. In Asia, pit vipers of the Ovophis species complex are medically important venomous snakes whose venom properties have not been investigated in depth. This study characterized the venom proteomes of Ovophis convictus (West Malaysia), Ovophis tonkinensis (northern Vietnam, southern China), and Ovophis okinavensis (Okinawa, Japan) by applying liquid chromatography-tandem mass spectrometry, which detected a high abundance of snake venom serine proteases (SVSP, constituting 40–60% of total venom proteins), followed by phospholipases A2, snake venom metalloproteinases of mainly P-III class, L-amino acid oxidases, and toxins from other protein families which were less abundant. The venoms exhibited different procoagulant activities in human plasma, with potency decreasing from O. tonkinensis > O. okinavensis > O. convictus. The procoagulant nature of venom confirms that consumptive coagulopathy underlies the pathophysiology of Ovophis pit viper envenomation. The hetero-specific antivenoms Gloydius brevicaudus monovalent antivenom (GbMAV) and Trimeresurus albolabris monovalent antivenom (TaMAV) were immunoreactive toward the venoms, and cross-neutralized their procoagulant activities, albeit at variably limited efficacy. In the absence of species-specific antivenom, these hetero-specific antivenoms may be useful in treating coagulotoxic envenomation caused by the different snakes in their respective regions.

“…Toxin families within the Daboia genus are dominated by PLA 2 and svMP, whereas the CTL content varies in strong dependence on the region of origin [ 68 , 89 , 90 , 91 , 92 , 93 ]. Interestingly, it seems that the amount of svSP slightly increases from the western to the eastern Daboia distributions and that KUN are less abundant in the most southern Asian populations ( D. russelii : south India, Sri Lanka; and D. siamensis : Indonesia) ( Supplementary Material Figure S2A ).…”

Section: Venom Variations Of Old World Vipersmentioning

confidence: 99%

“…Some publications list several of those quantified venom proteomes, but Viperinae-related studies in particular constitute only a small part [ 61 , 62 , 63 ]. Although no up-to-date database summarizes all of these Viperinae studies in a comprehensive manner, there are a certain number of publications reviewing Viperinae venoms, that only focus on a few genera of high medical relevance or from exclusive areas [ 19 , 64 , 65 , 66 , 67 , 68 ]. However, there are many more studies on true vipers containing fully investigated venoms at the proteomic level.…”

Section: Introductionmentioning

confidence: 99%

Old World Vipers—A Review about Snake Venom Proteomics of Viperinae and Their Variations

Damm

Hempel

Süssmuth

2021

Toxins

Fine-tuned by millions of years of evolution, snake venoms have frightened but also fascinated humanity and nowadays they constitute potential resources for drug development, therapeutics and antivenoms. The continuous progress of mass spectrometry techniques and latest advances in proteomics workflows enabled toxinologists to decipher venoms by modern omics technologies, so-called ‘venomics’. A tremendous upsurge reporting on snake venom proteomes could be observed. Within this review we focus on the highly venomous and widely distributed subfamily of Viperinae (Serpentes: Viperidae). A detailed public literature database search was performed (2003–2020) and we extensively reviewed all compositional venom studies of the so-called Old-World Vipers. In total, 54 studies resulted in 89 venom proteomes. The Viperinae venoms are dominated by four major, four secondary, six minor and several rare toxin families and peptides, respectively. The multitude of different venomics approaches complicates the comparison of venom composition datasets and therefore we differentiated between non-quantitative and three groups of quantitative workflows. The resulting direct comparisons within these groups show remarkable differences on the intra- and interspecies level across genera with a focus on regional differences. In summary, the present compilation is the first comprehensive up-to-date database on Viperinae venom proteomes and differentiating between analytical methods and workflows.