Unveiling the nature of black mamba (Dendroaspis polylepis) venom through venomics and antivenom immunoprofiling: Identification of key toxin targets for antivenom development

High-throughput immuno-profiling of mamba (Dendroaspis) venom toxin epitopes using high-density peptide microarrays

“…Key findings within the most important toxin families in mamba and cobra venoms are presented in the following subsections, where focus is directed on toxins of high medical importance as judged by their Toxicity Scores determined in previous studies2122.…”

“…One of the most important toxin groups contributing to the high lethality of the venoms of many elapids, including D. polylepis , is the short chain (type 1) α-neurotoxins22, of which four originate from mamba and five from cobra species. For this group of α-neurotoxins, the most noticeable residue scores and effects of substitution for alanine were observed for the motif DHRG found in the alignment from position 34 to 37.…”

“…Mamba envenomings are known for their rapid onset of neurotoxicity1920, which may manifest itself already after 15 min via clinical signs such as flaccid paralysis, dyspnea due to respiratory muscle paralysis, and involuntary skeletal muscle contractions or fasciculations19. These effects are explained by the venom compositions, which are dominated by potent small neurotoxins belonging to the three-finger toxin family and Kunitz-type serine protease inhibitor family212223. α-neurotoxins bind to nicotinic cholinergic receptors at the motor end-plate of muscle fibers, thereby blocking neuromuscular transmission24.…”

“…In addition, fasciculins, which are inhibitors of acetylcholinesterase (AChE), have been isolated from D. angusticeps venom, and these quite unique AChE inhibitors may induce increased synaptic concentrations of acetylcholine causing fasciculation26. Although many toxins have been isolated and sequenced from Dendroaspis venoms, only the venoms of D. polylepis and D. angusticeps have so far undergone a thorough toxicovenomics analysis2122. In spite of the significant differences in venom compositions, many similar toxins exist in Dendroaspis venoms, although in different relative proportions, which is to be expected given the phylogenetic proximity of the four species27.…”

Small Molecule Therapeutics for the Initial and Adjunctive Treatment of Snakebite

“…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]. 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.…”