News Archive

Sicarius terrosus (six-eyed cave spider) is a highly toxic (and somewhat infamous) spider of the sicariidae family, whose bites, however rare, are characterised by significant necrotic pathology and potential mortality.  This is largely because of the presence of sphingomyelinase D in its venom[1], in the form of Phospholipase D StSicTox-betaIC1[2].  This has been shown to cause dermonecrosis in mammals[3] as well as being a potent insecticide[4].  Additionally an StSicTox-beta IF1 variant is present, which similarly catalyses sphingomyelin hydrolysis[5], does so with low effectiveness and does not cause dermonecrosis, blood vessel permeability and platelet aggregation.  Two cytochrome C oxidase subunits[6][7] (catalyses reduction of O₂ to H₂O) are found in this venom, as well as reserves of NADH dehydrogenase[8].

[1] http://www.ncbi.nlm.nih.gov/pubmed/23991242

[2] http://www.uniprot.org/uniprot/C1ITQ4

[3] http://www.ncbi.nlm.nih.gov/pubmed/19042943

[4] http://www.ncbi.nlm.nih.gov/pubmed/22561243

[5] http://www.uniprot.org/uniprot/C0JB54

[6] http://www.uniprot.org/uniprot/C1ITQ4

[7] http://www.uniprot.org/uniprot/C1ITQ3

[8] http://www.uniprot.org/uniprot/B8R334

Naja Pallida is a species of Elapid (cobra) found across Africa.  Naja pallida venom, like that of most spitting cobras, is a cocktail of neurotoxins and cytotoxins, with a murine LD ₅₀ of 2mg/kg (intraperitoneal). Components contained within this cobra venom include Cytotoxin 1 (CX1_NAJPA)[1], which binds to cell membranes and depolarises cardiomyocytes, as well as inhibiting protein kinases C, and binding to integrin alpha-V/beta-3.  It can also lyse a wide range of cells including red blood cells and induces pore formation in cell membranes.  Another cytotoxic component in Naja pallida venom is basic phospholipase A2 nigexine (PA2B_NAJPA)[2], an anticoagulant enzyme that affects neuromuscular transmission in vitro.  Neurotoxic components include short neurotoxin 1 (NXS1_NAJPA)[3], which binds with high affinity to muscular nicotinic acetylcholine receptors (nAChRs), but has a low affinity for the alpha 7 nAChRs, which are important in working memory and cognition. Antagonism of nicotinic acetylcholine receptors causes flaccid paralysis by post-synaptic blockage of neuromuscular transmission.

[1] http://www.uniprot.org/uniprot/P01468

[2] http://www.uniprot.org/uniprot/P14556

[3] http://www.uniprot.org/uniprot/P01426

Agkistrodon contortrix (Copperhead snake) is a North American pit viper with a venom that causes significant coagulopathy in its prey.  Largely haematological in target, proteins in Agkistrodon contortrix venom include those associated with the clotting process such as Protein C Activator[1] that selectively cleaves protein C (a Factor Va activator), the thrombin-like enzyme contortrixobin (cleaves fibrinogen beta-chain causing fibrin precipitation), and the disintegrins acostatin-alpha (inhibits platelet aggregation)[2] as well as several other disintegrins that have not been fully described as of yet. 

Agkistrodon contortrix venom is also rich in Snake Venom Metalloproteinases (SVMP) such as Fibrolase[3] and ACLF[4] which exhibit fibrinolytic activity, and zinc metalloproteinase-disintegrin-like ACLD[5] which activates prothrombin (F2) whilst showing poor binding of collagen, activating procoagulant cell responses, induces the release of von Willebrand factor and nitric oxide but does not cause apoptosis.  The well-known protein contortrostatin[6] is also present, that blocks cancer cell adhesion to fibronectin and vitronectin, preventing invasion and  metastasis.

[1] http://www.uniprot.org/uniprot/P09872

[2] http://www.uniprot.org/uniprot/Q805F7

[3] http://www.uniprot.org/uniprot/P28891

[4] http://www.uniprot.org/uniprot/Q92031

[5] http://www.uniprot.org/uniprot/O42138

[6] http://www.uniprot.org/uniprot/Q9IAB0

Latrodectus tredecimguttatus (13 spot widow) is an areneomorph spider found in the Mediterranean and surrounding areas.  It is considered medically significant like all Latrodectus venom and utilises a variety of potentially significant components.  Alpha-latrotoxin, a presynaptic neurotoxin that induces exhaustive neurotransmitter release[1] is one of these, shown to bind to Latrophilin GPCRs[2] (mutations of which are a key risk factor in ADHD) and neurexin-1-alpha.  Delta- and Alpha-latroinsectotoxin, also present, have a similar mechanism of action, however have effect only on invertebrate neuromuscular junctions and not mammalian[3], as well as hitting tyrosine-protein phosphatase S receptor types (PTPRS)[4].  Alpha-Latrocrustotoxin-Lt1a, another key component, hits the same targets as latroinsectotoxin but is selective to crustaceans[5].  Additionally, Latrodectus bites have been known to cause myocardial damage, indicating a little-studied cardiac effect[6].

[1] http://www.uniprot.org/uniprot/P23631

[2] http://www.ncbi.nlm.nih.gov/pubmed/24739570

[3] http://www.uniprot.org/uniprot/Q25338

[4] http://www.uniprot.org/uniprot/Q02989

[5] http://www.uniprot.org/uniprot/Q9XZC0

[6] http://www.ncbi.nlm.nih.gov/pubmed/9834868

Deinagkistrodon acutus (Hundred-pace pit viper) is a viper species from Southeast Asia with a hemotoxic venom.  The venom of this snake is well characterised with many proteins described including several metalloproteinases[1][2], non-lethal platelet aggregation inhibitors[3][4], angiogenic proteins[5][6], and a thrombin-like enzyme that shows reduction in brain injury in hyperglycemic rats[7].  The venom is highly procoagulant due to the presence of several defibrinating proteins such as Agacutase[8] and AVVC-1[9], which shows potential apoptotic activity against human leukaemia cells.

[1] http://www.uniprot.org/uniprot/Q9PW35

[2] http://www.uniprot.org/uniprot/P60244

[3] http://www.uniprot.org/uniprot/Q9DEF8

[4] http://www.uniprot.org/uniprot/Q9IAM1

[5] http://www.uniprot.org/uniprot/Q8AYA3

[6] http://www.uniprot.org/uniprot/Q8JIV9

[7] http://www.ncbi.nlm.nih.gov/pubmed/15353234

[8] http://www.ncbi.nlm.nih.gov/pubmed/23429184

[9] http://www.ncbi.nlm.nih.gov/pubmed/23815904