Selecting key toxins for focused development of elapid snake antivenoms and inhibitors guided by a Toxicity Score

Laustsen, Andreas Hougaard; Lohse, Brian; Lomonte, Bruno; Engmark, Mikael; Gutiérrez, José Marı́a

doi:10.1016/j.toxicon.2015.07.334

Cited by 80 publications

(75 citation statements)

References 16 publications

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“… Tested with both: o Minimum acceptable: Pre-mixing of venom and antidote prior to injection (ED50 determination) [27] o Ideal: Venom administration prior to administration of antidote [6,26,40] Broad Spectrum  Depending on target selection (ubiquity and medical importance of inhibitory target among snake species) [41,42] Heat Stable  Real-time stability studies up to 30 °C (±2 °C) and relative humidity of 75% (±5%) (WHO "Climatic Zone IVb") [ …”

Section: Efficacy (In Vivo)mentioning

confidence: 99%

“…Thus, SMT targets for inhibition should be, ideally, abundant across as many of the medically important snake species as possible. For understanding venom properties and targeting, proteomic analysis of snake venom has been crucial to reveal species variation in venom composition and toxicity [41,47,48]. Proteomic analysis has revealed a wide array of active toxic ingredients from at least 26 protein families, but the most common medically relevant components are found within four families in varying proportions [49][50][51].…”

Section: Venom Target Selectionmentioning

confidence: 99%

“…Proteomic analysis has revealed a wide array of active toxic ingredients from at least 26 protein families, but the most common medically relevant components are found within four families in varying proportions [49][50][51]. These proteins are the phospholipase A2 (PLA2s), snake venom metallo-and serine-proteases (svMPs and SPs, respectively), and the non-enzymatic three-finger toxins (3-FTX) [41,[50][51][52]. Not all snake venoms, however, have unique toxins that are in this group of four, including mambas with dendrotoxins and some rattlesnakes with low molecular mass cationic myotoxins [53][54][55].…”

Section: Venom Target Selectionmentioning

confidence: 99%

“…Continued research into the proteomic and toxicovenomic characterization of the most medically relevant venoms are crucial in order to have a more comprehensive understanding of drug and antivenom targeting in these species, as well as to understand the nature of therapeutic failures when they occur. The use of tools, such as the newly developed Toxicity Score, which combines the medical importance and the relative abundance of a specific toxin, can aid the identification of a target [41,42].…”

Section: Venom Target Selectionmentioning

confidence: 99%

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Small Molecule Therapeutics for the Initial and Adjunctive Treatment of Snakebite

Bulfone¹,

Samuel²,

Bickler³

et al. 2018

Preprint

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Abstract:The World Health Organization (WHO) recently added snakebite envenoming to the priority list of Neglected Tropical Diseases (NTD). It is thought that ~75% of mortality following snakebite occurs outside the hospital setting, making the temporal gap between a bite and antivenom administration a major therapeutic challenge. Small molecule therapeutics (SMTs) have been proposed as potential pre-referral treatments for snakebite to help address this gap. Herein, we discuss the characteristics, potential uses and development of SMTs as potential treatments for snakebite envenomation. We focus on SMTs that are secretory phospholipase A2 (sPLA2) inhibitors and metalloprotease (MP) inhibitors.

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Section: Efficacy (In Vivo)mentioning

confidence: 99%

Section: Venom Target Selectionmentioning

confidence: 99%

Section: Venom Target Selectionmentioning

confidence: 99%

Section: Venom Target Selectionmentioning

confidence: 99%

See 2 more Smart Citations

Small Molecule Therapeutics for the Initial and Adjunctive Treatment of Snakebite

Bulfone¹,

Samuel²,

Bickler³

et al. 2018

Preprint

View full text Add to dashboard Cite

show abstract

“…Last year, Gutiérrez and his colleagues separated and identified the most toxic proteins from a family of venomous snakes known as elapids (Elapidae). By combining information about the abundance of each protein and how lethal it is to mice, the team created a toxicity score to indicate how important it was to neutralize a protein with antivenom, a first step towards making the treatment 3 .…”

Section: Old Problem New Solutionmentioning

confidence: 99%

Vipers, mambas and taipans: the escalating health crisis over snakebites

Arnold¹

2016

Nature

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The application of laboratory‐based analytical tools and techniques for the quality assessment and improvement of commercial antivenoms used in the treatment of snakebite envenomation

Patra

Herrera

Gutiérrez

et al. 2021

Drug Testing and Analysis

Self Cite

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Snakebite envenomation is a public health problem of high impact, particularly for the developing world. Antivenom, which contains whole or protease‐digested immunoglobulin G, purified from the plasma of hyper‐immunized animals (mainly horses), is the mainstay for the treatment of snakebite envenomation. The success of antivenom therapy depends upon its ability to abrogate or reduce the local and systemic toxicity of envenomation. In addition, antivenom administration must be safe for the patients. Therefore, antivenom manufacturers must ensure that these products are effective and safe in the treatment of envenomations. Antivenom efficacy and safety are determined by the physicochemical characteristics of formulations, purity of the immunoglobulin fragments and antibodies, presence of protein aggregates, endotoxin burden, preservative load, and batch to batch variation, as well as on the ability to neutralize the most important toxins of the venoms against which the antivenom is designed. In this context, recent studies have shown that laboratory‐based simple analytical techniques, for example, size exclusion chromatography, sodium dodecyl sulphate polyacrylamide gel electrophoresis, mass spectrometry, immunological profiling including immuno‐turbidimetry and enzyme‐linked immunosorbent assays, Western blotting, immune‐chromatographic technique coupled to mass spectrometry analysis, reverse‐phase high performance liquid chromatography, spectrofluorometric analysis, in vitro neutralization of venom enzymatic activities, and other methodologies, can be applied for the assessment of antivenom quality, safety, stability, and efficacy. This article reviews the usefulness of different analytical techniques for the quality assessment of commercial antivenoms. It is suggested that these tests should be applied for screening the quality of commercial antivenoms before their preclinical and clinical assessment.

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Selecting key toxins for focused development of elapid snake antivenoms and inhibitors guided by a Toxicity Score

Cited by 80 publications

References 16 publications

Small Molecule Therapeutics for the Initial and Adjunctive Treatment of Snakebite

Small Molecule Therapeutics for the Initial and Adjunctive Treatment of Snakebite

Vipers, mambas and taipans: the escalating health crisis over snakebites

The application of laboratory‐based analytical tools and techniques for the quality assessment and improvement of commercial antivenoms used in the treatment of snakebite envenomation

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