Proteomics and antivenomics of Echis carinatus carinatus venom: Correlation with pharmacological properties and pathophysiology of envenomation

Patra, Aparup; Kalita, Bhargab; Chanda, Abhishek; Mukherjee, Ashis K.

doi:10.1038/s41598-017-17227-y

Cited by 87 publications

(152 citation statements)

References 65 publications

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“…Viper snaclecs are one of the most abundant nonenzymatic group of proteins in some Viperidae venoms [8][9][10][11][12]. The Snaclecs reduced the exploratory behavior and locomotor activity of pheasant chicks as well as mice within 5 min of injection in a concentration-dependent manner, as shown in Figure 1.…”

Section: Discussionmentioning

confidence: 87%

“…Snake C-type lectin-like proteins (snaclecs) are mainly expressed in the venoms of vipers and colubrids [4,5]. The available data indicates that snaclecs may be one of the most abundant nonenzymatic group of proteins in the venoms [8][9][10][11][12][13]. Snalecs usually have a heterodimeric structure with α and β subunits, which are often oligomerized to form protein multimers, and have evolved to bind a wide range of physiologically important proteins such as GPIb, GPVI and integrins on mammal platelets [13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

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Snake C-Type Lectins Potentially Contribute to the Prey Immobilization in Protobothrops mucrosquamatus and Trimeresurus stejnegeri Venoms

Tian

Liu

et al. 2020

Toxins

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Snake venoms contain components selected to immobilize prey. The venoms from Elapidae mainly contain neurotoxins, which are critical for rapid prey paralysis, while the venoms from Viperidae and Colubridae may contain fewer neurotoxins but are likely to induce circulatory disorders. Here, we show that the venoms from Protobothrops mucrosquamatus and Trimeresurus stejnegeri are comparable to those of Naja atra in prey immobilization. Further studies indicate that snake C-type lectin-like proteins (snaclecs), which are one of the main nonenzymatic components in viper venoms, are responsible for rapid prey immobilization. Snaclecs (mucetin and stejnulxin) from the venoms of P. mucrosquamatus and T. stejnegeri induce the aggregation of both mammalian platelets and avian thrombocytes, leading to acute cerebral ischemia, and reduced animal locomotor activity and exploration in the open field test. Viper venoms in the absence of snaclecs fail to aggregate platelets and thrombocytes, and thus show an attenuated ability to cause cerebral ischemia and immobilization of their prey. This work provides novel insights into the prey immobilization mechanism of Viperidae snakes and the understanding of viper envenomation-induced cerebral infarction.

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Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Snake C-Type Lectins Potentially Contribute to the Prey Immobilization in Protobothrops mucrosquamatus and Trimeresurus stejnegeri Venoms

Tian

Liu

et al. 2020

Toxins

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show abstract

“…In these experiments, mice were challenged with venom intraperitoneally followed by delayed dosing of the marimastat and varespladib inhibitor mix 15 mins later, as previously described 28 63 , Echis carinatus (India) 68 , Bothrops asper (Costa Rica, "Atlantic") 69 , Bitis arietans (Nigeria) 70 and Daboia russelii (Sri Lanka) 64 Note the different y-axis scales.…”

Section: Preclinical Efficacy Via a 'Challenge Then Treat' Model Of Ementioning

confidence: 99%

A therapeutic combination of two small molecule toxin inhibitors provides pancontinental preclinical efficacy against viper snakebite

Albulescu

Xie²,

Ainsworth³

et al. 2020

Preprint

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Snakebite is a medical emergency causing high mortality and morbidity in rural tropical communities that typically experience delayed access to unaffordable therapeutics. Viperid snakes are responsible for the majority of envenomings, but extensive interspecific variation in venom composition dictates that different antivenom treatments are used in different parts of the world, resulting in clinical and fiscal snakebite management challenges. Here, we show that a number of repurposed Phase 2-approved small molecules are capable of broadly neutralizing distinct viper venom bioactivities in vitro by inhibiting different enzymatic toxin families. Furthermore, using multiple in vivo models of envenoming, we demonstrate that a single dose of a rationally-selected dual inhibitor combination consisting of marimastat and varespladib prevents lethality caused by venom from the most medically-important vipers of Africa, South Asia and Central America. Our findings strongly support the translation of

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“…Map of saw-scaled viper distribution with the locales of the studied species indicated by red stars. Echis distribution areas and corresponding venom proteomes are highlighted by the following colors: light orange (E. leucogaster), blue (E. ocellatus (11)), green (E. carinatus), pink (E. pyramidum (11)), violet (E. coloratus (11) Toxin proteome abundances were taken from (11,57) and generated in this study for E. leucogaster. Toxin family key: SVMP, snake venom metalloproteinase; SVSP, snake venom serine proteinase; PLA2, phospholipase A2; CTL, Ctype lectins; LAAO, L-amino acid oxidase; SVMPi, SVMP inhibitors; DIS, disintegrin; CRISP, Cysteine-rich secretory protein.…”

Section: The Geographical Distribution and Venom Toxin Composition mentioning

confidence: 99%

Preclinical validation of a repurposed metal chelator as a community-based therapeutic for hemotoxic snakebite

Albulescu

Hale

Ainsworth

et al. 2019

Preprint

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Snakebite envenoming causes 138,000 deaths annually and ~400,000 victims are left with permanent disabilities. Envenoming by saw-scaled vipers (Viperidae: Echis) leads to systemic hemorrhage and coagulopathy, and represents a major cause of snakebite mortality and morbidity in Africa and Asia. The only specific treatment for snakebite, antivenom, has poor specificity, low affordability, and must be administered in clinical settings due to its intravenous delivery and high rates of adverse reactions. This requirement results in major treatment delays in resource-poor regions and impacts substantially on patient outcomes following envenoming.Here we investigated the value of metal chelators as novel community-based therapeutics for snakebite. Among the tested chelators, dimercaprol (British anti-Lewisite) and its derivative 2,3dimercapto-1-propanesulfonic acid (DMPS), were found to potently antagonize the activity of Zn 2+ -dependent snake venom metalloproteinase toxins in vitro. Moreover, DMPS prolonged or conferred complete survival in murine preclinical models of envenoming against a variety of saw-scaled viper venoms. DMPS also significantly extended survival in a 'challenge and treat' model, where drug administration was delayed post-venom injection, and the oral administration of this chelator provided partial protection against envenoming. Finally, the potential clinical scenario of early oral DMPS therapy combined with a later, delayed, intravenous dose of conventional antivenom provided prolonged protection against the lethal effects of envenoming in vivo. Our findings demonstrate that safe and affordable repurposed metal chelators effectively neutralize saw-scaled viper venoms in vitro and in vivo and highlight the great promise of DMPS as a novel, community-based, early therapeutic intervention for hemotoxic snakebite envenoming.

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Proteomics and antivenomics of Echis carinatus carinatus venom: Correlation with pharmacological properties and pathophysiology of envenomation

Cited by 87 publications

References 65 publications

Snake C-Type Lectins Potentially Contribute to the Prey Immobilization in Protobothrops mucrosquamatus and Trimeresurus stejnegeri Venoms

Snake C-Type Lectins Potentially Contribute to the Prey Immobilization in Protobothrops mucrosquamatus and Trimeresurus stejnegeri Venoms

A therapeutic combination of two small molecule toxin inhibitors provides pancontinental preclinical efficacy against viper snakebite

Preclinical validation of a repurposed metal chelator as a community-based therapeutic for hemotoxic snakebite

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