Purification, Characterization, and Chemical Modification of Neurotoxic Peptide from <i>Daboia russelii</i> Snake Venom of India

Venkatesh, Madhukumar; Prasad, Nagarajan Rajendra; Sing, Tej; Gowda, Veerabasappa T.

doi:10.1002/jbt.21486

Cited by 14 publications

(6 citation statements)

References 28 publications

(36 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Tandem mass spectrometry of venom fractions (n = 10) from these samples identified between 49 and 66 proteins from 13 toxin families, including phospholipase A 2 (PLA 2 ), Kunitz-type serine protease inhibitor (Kunitz), snake venom serine protease (SVSP), cysteinerich secretory protein (CRISP), snaclec, snake venom metalloproteinase (SVMP), three-finger toxin [3FTx; neurotoxic-3FTx (N-3FTx) and cytotoxic-3FTx (C-3FTx)], L-amino-acid oxidase ). The identification of 3FTx in Daboia venoms is particularly noteworthy as these toxins are rarely reported in the venom proteomes of viperid snakes [36,37].…”

Section: Venom Proteomicsmentioning

confidence: 99%

Biogeographic venom variation in Russell’s viper (Daboia russelii) and the preclinical inefficacy of antivenom therapy in snakebite hotspots

et al. 2021

View full text Add to dashboard Cite

Background Snakebite in India results in over 58,000 fatalities and a vast number of morbidities annually. The majority of these clinically severe envenomings are attributed to Russell’s viper (Daboia russelii), which has a near pan-India distribution. Unfortunately, despite its medical significance, the influence of biogeography on the composition and potency of venom from disparate D. russelii populations, and the repercussions of venom variation on the neutralisation efficacy of marketed Indian antivenoms, remain elusive. Methods Here, we employ an integrative approach comprising proteomic characterisation, biochemical analyses, pharmacological assessment, and venom toxicity profiling to elucidate the influence of varying ecology and environment on the pan-Indian populations of D. russelii. We then conducted in vitro venom recognition experiments and in vivo neutralisation assays to evaluate the efficacy of the commercial Indian antivenoms against the geographically disparate D. russelii populations. Findings We reveal significant intraspecific variation in the composition, biochemical and pharmacological activities and potencies of D. russelii venoms sourced from five distinct biogeographic zones across India. Contrary to our understanding of the consequences of venom variation on the effectiveness of snakebite therapy, commercial antivenom exhibited surprisingly similar neutralisation potencies against the majority of the investigated populations, with the exception of low preclinical efficacy against the semi-arid population from northern India. However, the ability of Indian antivenoms to counter the severe morbid effects of Daboia envenoming remains to be evaluated. Conclusion The concerning lack of antivenom efficacy against the north Indian population of D. russelii, as well as against two other ‘big four’ snake species in nearby locations, underscores the pressing need to develop pan-India effective antivenoms with improved efficacy in high snakebite burden locales.

show abstract

Section: Venom Proteomicsmentioning

confidence: 99%

Biogeographic venom variation in Russell’s viper (Daboia russelii) and the preclinical inefficacy of antivenom therapy in snakebite hotspots

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Although significant research has focused on the neurotoxic effects of venoms, comparatively little work has been done on the coagulotoxic effects of snake species due to the inherent difficulties in working with blood without the use of advanced robotics such as that utilized in this study [15,16,17]. Venoms acting upon the blood are often utilized by species which predate upon mammals, effectively disrupting hemostasis within the body leading to hemorrhagic shock or stroke [18,19].…”

Section: Introductionmentioning

confidence: 99%

Venomous Landmines: Clinical Implications of Extreme Coagulotoxic Diversification and Differential Neutralization by Antivenom of Venoms within the Viperid Snake Genus Bitis

Youngman

Debono

Dobson

et al. 2019

Toxins

View full text Add to dashboard Cite

The genus Bitis comprises 17 snake species that inhabit Africa and the Arabian Peninsula. They are responsible for a significant proportion of snakebites in the region. The venoms of the two independent lineages of giant Bitis (B. arietans and again in the common ancestor of the clade consisting of B. gabonica, B. nasicornis, B. parviocula and B. rhinoceros) induce an array of debilitating effects including anticoagulation, hemorrhagic shock and cytotoxicity, whilst the dwarf species B. atropos is known to have strong neurotoxic effects. However, the venom effects of the other species within the genus have not been explored in detail. A series of coagulation assays were implemented to assess the coagulotoxic venom effects of fourteen species within the genus. This study identified procoagulant venom as the ancestral condition, retained only by the basal dwarf species B. worthingtoni, suggesting anticoagulant venom is a derived trait within the Bitis genus and has been secondarily amplified on at least four occasions. A wide range of anticoagulant mechanisms were identified, such as coagulant and destructive activities upon fibrinogen in both giant and dwarf Bitis and the action of inhibiting the prothrombinase complex, which is present in a clade of dwarf Bitis. Antivenom studies revealed that while the procoagulant effects of B. worthingtoni were poorly neutralized, and thus a cause for concern, the differential mechanisms of anticoagulation in other species were all well neutralized. Thus, this study concludes there is a wide range of coagulotoxic mechanisms which have evolved within the Bitis genus and that clinical management strategies are limited for the procoagulant effects of B. worthingtoni, but that anticoagulant effects of other species are readily treated by the South African polyvalent antivenom. These results therefore have direct, real-work implications for the treatment of envenomed patients.

show abstract

“…A number of studies had been made on snake venoms and their isolated protein components for investigating the neurotoxic and myotoxic effects [24–32]. It was well-known that not only the neurotoxins and the myotoxins were extensively discovered as the main components in the venoms of Elapidae as well as Hydrophiidea, but also recently they were found as the minor components in the venoms of Viperidae and Crotalidae, especially Colubridae.…”

Section: Discussionmentioning

confidence: 99%

Dacin, one metalloproteinase from Deinagkistrodon acutus venom inhibiting contraction of mouse ileum muscle

Zhou

Liu

et al. 2017

BMC Biochem

View full text Add to dashboard Cite

BackgroundMice were bitten by five-pace vipers (Deinagkistrodon acutus), and then envenomed. It was well-known that the snake venom mainly disturbed the blood homeostasis of the envenomed victims. Ocassionally, we found that the venom of D. acutus could inhibit the contraction tension of mouse ileum, so in this study we aimed to identify the active component inhibiting the contraction tension of mouse ileum in the snake venom.ResultsThe active component inhibiting the contraction tension of mouse ileum, designated as Dacin, was isolated from D. acutus venom, purified to protein homogeneity and composed of a single peptide chain, about 23 kDa analyzed by SDS-PAGE, and 22, 947. 9 Da measured by MALDI-TOF-MS. Not only the results of its PMF blasted by Mascot indicated that Dacin may be one snake venom metalloproteinase (SVMP), but also the results of the biochemical and in-vivo assays as follow demonstrated that it was one SVMP: it cleaved Aα and Bβ chains, not Cγ of bovine fibrinogen within 1 h, and also hydrolyzed fibrin polymer; besides its fibrino(geno)lytic activities were strongly inhibited by β- mercaptoethanol, EDTA and EGTA; and it could induce a hemorrhagic reaction under the dorsal skin of mouse. In the isolated tissue assays, Dacin caused the concentration-dependent and time-dependent inhibitory actions on the spontaneous contraction tension of the ileum smooth muscle of mouse, and the inhibitory effects were irreversible.ConclusionsTaken together, for the first time one active component (Dacin, a SVMP) that irreversibly inhibited the spontaneous contraction tension of mouse ileum has been isolated and identified from D. acutus venom. The findings may provide not only a new insight for toxicological researches on SVMPs and venoms of the vipers, but also a reference for clinicians to treat the snake-bitten victims. However, Dacin’s inhibitory molecular mechanism will be further studied in the future.

show abstract

Purification, Characterization, and Chemical Modification of Neurotoxic Peptide from Daboia russelii Snake Venom of India

Cited by 14 publications

References 28 publications

Biogeographic venom variation in Russell’s viper (Daboia russelii) and the preclinical inefficacy of antivenom therapy in snakebite hotspots

Biogeographic venom variation in Russell’s viper (Daboia russelii) and the preclinical inefficacy of antivenom therapy in snakebite hotspots

Venomous Landmines: Clinical Implications of Extreme Coagulotoxic Diversification and Differential Neutralization by Antivenom of Venoms within the Viperid Snake Genus Bitis

Dacin, one metalloproteinase from Deinagkistrodon acutus venom inhibiting contraction of mouse ileum muscle

Contact Info

Product

Resources

About