EC-PIII, a novel non-hemorrhagic procoagulant metalloproteinase: Purification and characterization from Indian Echis carinatus venom

Choudhury, Manisha; Suvilesh, Kanve Nagaraj; Vishwanath, Bannikuppe S.; Velmurugan, D.

doi:10.1016/j.ijbiomac.2017.08.006

Cited by 10 publications

(11 citation statements)

References 26 publications

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“…We identified 3–7.4% of SVSPs in the two Echis subspecies and detected appreciable proteolytic activity. Echis venoms have been previously shown to induce blood coagulation via prothrombin activating PIII SVMPs [74]. Furthermore, in our experiments, Echis venoms also displayed tremendous fibrinogenolytic activity, cleaving both Aα and Bβ subunits of the human fibrinogen in under 5 mins, which is also likely to contribute to their extreme procoagulant effects (S2 Fig) [75, 76].…”

Section: Discussionsupporting

confidence: 51%

Beyond the ‘big four’: Venom profiling of the medically important yet neglected Indian snakes reveals disturbing antivenom deficiencies

et al. 2019

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BackgroundSnakebite in India causes the highest annual rates of death (46,000) and disability (140,000) than any other country. Antivenom is the mainstay treatment of snakebite, whose manufacturing protocols, in essence, have remained unchanged for over a century. In India, a polyvalent antivenom is produced for the treatment of envenomations from the so called ‘big four’ snakes: the spectacled cobra (Naja naja), common krait (Bungarus caeruleus), Russell’s viper (Daboia russelii), and saw-scaled viper (Echis carinatus). In addition to the ‘big four’, India is abode to many other species of venomous snakes that have the potential to inflict severe clinical or, even, lethal envenomations in their human bite victims. Unfortunately, specific antivenoms are not produced against these species and, instead, the ‘big four’ antivenom is routinely used for the treatment.MethodsWe characterized the venom compositions, biochemical and pharmacological activities and toxicity profiles (mouse model) of the major neglected yet medically important Indian snakes (E. c. sochureki, B. sindanus, B. fasciatus, and two populations of N. kaouthia) and their closest ‘big four’ congeners. By performing WHO recommended in vitro and in vivo preclinical assays, we evaluated the efficiencies of the commercially marketed Indian antivenoms in recognizing venoms and neutralizing envenomations by these neglected species.FindingsAs a consequence of dissimilar ecologies and diet, the medically important snakes investigated exhibited dramatic inter- and intraspecific differences in their venom profiles. Currently marketed antivenoms were found to exhibit poor dose efficacy and venom recognition potential against the ‘neglected many’. Premium Serums antivenom failed to neutralise bites from many of the neglected species and one of the ‘big four’ snakes (North Indian population of B. caeruleus).ConclusionsThis study unravels disturbing deficiencies in dose efficacy and neutralisation capabilities of the currently marketed Indian antivenoms, and emphasises the pressing need to develop region-specific snakebite therapy for the ‘neglected many’.

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Section: Discussionsupporting

confidence: 51%

Beyond the ‘big four’: Venom profiling of the medically important yet neglected Indian snakes reveals disturbing antivenom deficiencies

et al. 2019

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“…Some SVMPs and SVSPs are used as anticoagulant agents to treat ischemic strokes [ 29 ], peripheral arterial occlusions [ 30 ], and acute cerebral infarction [ 31 ] due to their capacity to degrade the extracellular matrix and hemostasis-related proteins, such as collagens, fibrinogen, and fibrin [ 32 , 33 , 34 ]. More importantly, due to their similarity to human MMPs [ 35 ], snake venom proteases are potential wound-healing therapeutics as they can participate as procoagulants/platelet aggregators [ 36 , 37 , 38 , 39 , 40 ], inflammation modulators [ 41 , 42 , 43 , 44 ], cell migration stimulators, cell proliferators [ 45 , 46 ], skin fibroblasts activators [ 47 ], cell migration factors [ 48 , 49 ], angiogenesis enhancers [ 36 , 38 ], and activators of MMP-2 and MMP-9 [ 50 , 51 , 52 ].…”

Section: Introductionmentioning

confidence: 99%

Functional Mining of the Crotalus Spp. Venom Protease Repertoire Reveals Potential for Chronic Wound Therapeutics

et al. 2020

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Chronic wounds are a major health problem that cause millions of dollars in expenses every year. Among all the treatments used, active wound treatments such as enzymatic treatments represent a cheaper and specific option with a fast growth category in the market. In particular, bacterial and plant proteases have been employed due to their homology to human proteases, which drive the normal wound healing process. However, the use of these proteases has demonstrated results with low reproducibility. Therefore, alternative sources of proteases such as snake venom have been proposed. Here, we performed a functional mining of proteases from rattlesnakes (Crotalus ornatus, C. molossus nigrescens, C. scutulatus, and C. atrox) due to their high protease predominance and similarity to native proteases. To characterize Crotalus spp. Proteases, we performed different protease assays to measure and confirm the presence of metalloproteases and serine proteases, such as the universal protease assay and zymography, using several substrates such as gelatin, casein, hemoglobin, L-TAME, fibrinogen, and fibrin. We found that all our venom extracts degraded casein, gelatin, L-TAME, fibrinogen, and fibrin, but not hemoglobin. Crotalus ornatus and C. m. nigrescens extracts were the most proteolytic venoms among the samples. Particularly, C. ornatus predominantly possessed low molecular weight proteases (P-I metalloproteases). Our results demonstrated the presence of metalloproteases capable of degrading gelatin (a collagen derivative) and fibrin clots, whereas serine proteases were capable of degrading fibrinogen-generating fibrin clots, mimicking thrombin activity. Moreover, we demonstrated that Crotalus spp. are a valuable source of proteases that can aid chronic wound-healing treatments.

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“…The aim of this project was to develop a fluorescence bioassay to detect individual proteases in snake venoms following chromatographic separation and fractionation. Studies relating to snake venom protease activity have traditionally relied on casein-based protease substrates such as casein-FITC (Arpitha et al, 2017;Borges et al, 2001;Choudhury et al, 2017;Cupp-Enyard, 2009;Delpierre, 1968;Mukherjee, 2008;Yee et al, 2016). This is partly because casein is widely available and targeted by a vast range of proteases, making it a generic substrate.…”

Section: Resultsmentioning

confidence: 99%

“…This can be explained by variation in venom toxin composition being ubiquitous among snake species (Casewell et al, 2014;Slagboom et al, 2017;Tasoulis and Isbister, 2017). All of the studied snake species produce hemotoxic venoms rich in proteases, but the number of these toxins, their relative abundance, and the ratio of serine proteases to metalloproteases varies among the species (Casewell et al, 2009;Choudhury et al, 2017;Pahari et al, 2007;Sanz et al, 2008).…”

Section: Assignment Of Bioactive Venom Proteasesmentioning

confidence: 99%

Development of a generic high-throughput screening assay for profiling snake venom protease activity after high-resolution chromatographic fractionation

Neumann

Slagboom

Somsen

et al. 2020

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EC-PIII, a novel non-hemorrhagic procoagulant metalloproteinase: Purification and characterization from Indian Echis carinatus venom

Cited by 10 publications

References 26 publications

Beyond the ‘big four’: Venom profiling of the medically important yet neglected Indian snakes reveals disturbing antivenom deficiencies

Beyond the ‘big four’: Venom profiling of the medically important yet neglected Indian snakes reveals disturbing antivenom deficiencies

Functional Mining of the Crotalus Spp. Venom Protease Repertoire Reveals Potential for Chronic Wound Therapeutics

Development of a generic high-throughput screening assay for profiling snake venom protease activity after high-resolution chromatographic fractionation

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