Toxin synergism in snake venoms

Abstract

Synergism between venom toxins exists for a range of snake species. Synergism can be derived from both intermolecular interactions and supramolecular interactions between venom components and can be the result of toxins targeting the same protein, biochemical pathway, or physiological process. Few simple systematic tools and methods for determining the presence of synergism exist, but include co-administration of venom components and assessment of Accumulated Toxicity Scores. A better understanding of how to investigate synergism in snake venoms may help unravel strategies for developing novel therapies against snakebite envenoming by elucidating mechanisms for toxicity and interactions between venom components.

Discovering venom-derived drug candidates using differential gene expression

“…Interestingly, PPARγ activation results in cellular protection from NMDA toxicity. Given the known inhibitory effect of argiotoxins on NMDA receptors [Moe et al, 1998], this is striking and biologically plausible evidence for toxin synergism, where two or more venom components target multiple cellular structures with related functions in order to incite a more powerful response [Laustsen, 2016].…”

“…Even though most existing venom-derived drugs consist of a single component, crude venoms in nature use the synergistic effects of multiple components to cause specific phenotypic effects [Laustsen, 2016]. Therefore, testing each venom component individually using the where n is the number of components in the venom).…”

Small Molecule Therapeutics for the Initial and Adjunctive Treatment of Snakebite

“…As put by Laustsen, snake venom is likely to be the "most complex pharmaceutical target" known, composed of a multitude of toxin components and complex biochemical interactions [42]. Thus, SMT targets for inhibition should be, ideally, abundant across as many of the medically important snake species as possible.…”

“…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].…”

“… 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") [ …”