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Summary
Covalitoxin-II is a peptide toxin, produced by the spider Coremiocnemis validus. The specific mode of action is still unclear. Experiments have shown that the toxin induces non-lethal excitatory behavioral symptoms (like quivering and jerking) in crickets.

Source
Covalitoxin-II (Cvtx-II) is isolated from the venom of the Coremiocnemis validus (Singapore or Blue femur tarantula). This spider lives in South East Asian tropical forests.

Structure
The toxin consists of 31 amino acids (ACSRAGENCYKSGRCCDGLYCKAYVVTCYKP). This sequence forms a peptide with a molecular weight of 3.4 kDa. It has six cysteine residues which form three disulphide bonds, between the specific amino acid locations 2&16, 19&21 and 15&28. There is an equal distribution of hydrophilic, hydrophobic and neutral amino acids. Near the C-terminus there is a positively charged surface formed by conserved basic residues, which interacts with ion channel.

Analogy to other toxins
The cystine motif that is formed by the cysteine residues shows analogy to other spider toxins. It is also analogous to ω-toxins, which is present in the venom of cone snails. The toxins of this family share a common structural motif. However, these toxins exhibit distinct effects by targeting different ionic channels.

There is low homology with two peptides:
 * 47% homology with spider peptide PLTX-II (calcium channel blocker)
 * 47% homology with conotoxin MrVIB (sodium channel blocker)

target and mode of action
The specific targets and mode of action of Cvtx-II on a molecular level are not clear yet. However, Cvtx-II shows similarities in structure and biological action with other conotoxins. The cystine motif of Cvtx-II is similar to 'ω-toxins' isolated from Conus venom and other spider toxins. These toxins affect the voltage-activated calcium channels. In some spider toxins the positively charged surface near the C-terminus of the toxin is responsible for ion channel interaction. Cvtx-II molecule also has this positively charged surface near the C-terminus. Therefore, a possible prediction of the mode of action of Cvtx-II is interaction of this positively charged surface with ion channel proteins. However, it is not known how this interaction takes place on a molecular level and whether this is the working mechanism of Cvtx-II.

Some excitoxins with the same biological action as Cvtx-II slow sodium current turn-off after an action potential in insects. These data support the hypothesis that excitotoxins like Cvtx-II modify the sodium channel inactivation mechanism.

Toxicity
Cvtx-II induces the following non-lethal symptoms in crickets:
 * Quivering, jerking, and hyperextension of the legs
 * Rapid movement of antenna, mandibles and maxillae
 * Abdominal contraction
 * Frequent body arching
 * Loss of righting reflex
 * Greatly reduced locomotion
 * Indications of paralysis

Experiments have shown that these symptoms are not in present in cockroaches or mice after Cvtx-II injections. Therefore, Cvtx-II is thought to be an insect-specific neurotoxic peptide. A dose of 0.2 µmol/g was necessary to immobilize or inactivate 50% of the insect.(ID50) After 40-60 minutes, the immobilizing effects gradually fully disappears.

Scientific relevance
Results of the experiments performed by Balaji et al. suggest that Cvtx-II is a species-specific insect toxin. Insect-selective excitatory toxins can be used to study pharmacology of ion channels in specific insects. Specific knowledge about this pharmacology is valuable for the design of insect-selective biopesticides, because it gains insight into the molecular mechanisms involved in reversible paralysis.