Agkistrodon (Moccasins & Cantils)
A. bilineatus - cantil
Bites by cantils produce massive localised edema, hemolysis and subsequent myonecrosis. Proteins partially responsible for these clinical symptoms have been isolated from the cantils: coagulant proteins (such as Bilineobin), hemorrhagic proteins (bilitoxin and HT-1), myonecrotic phospholipase A2s, and protein C activators.
Bilineobin is thrombin-like protease that contains a high degree of homology to batroxobin from Bothrops atrox and flavoxobin from Trimeresurus flavoviridis. Bilineobin catalyses the hydrolysis of arginine esters and thrombin substrates and has mild ability to convert fibrinogen to fibrin with the resultant production of fibrinopeptides.
The hemorrhagic bilitoxin does not effect the muscular intracellular junctions but does damage skeletal muscle cells and disrupts the capillary endothelium. This 48 kDa lethal hemorrhagic metalloproteinase cleaves first the alpha-chain and then the beta-chain of fibrinogen.
Hemorrhagic Toxin - 1 is a toxin possessing lethal, hemorrhagic and proteolytic activities. These activities of this toxin are inhibited by ethylenediaminetetraacetic acid (EDTA) and ethyleneglycol-bis- (beta-aminoethylether)N,N'-tetraacetic acid (EGTA), but not by cysteine or soybean trypsin inhibitor (SBTI). The A alpha chain of fibrinogen is first split and B beta chain was cleaved later by this toxin.
Phospholipases A2 from this species are myonecrotic, similar to PLA2s from Trimeresurus flavoviridis, A. c. contortrix, A. c. mokeson, A. p. piscivorus and Bothrops asper.
The venom also contains a protein C activator similar to that of protac from the southern copperhead (southern copperhead).
Agkistrodon contortrix (Copperheads)
The copperheads are considered non-life threatening, with bites resulting in massive edema and pain and being notable in producing the condition known as echymosis (sweating blood) where blood leads out of the pores and gums. Not fatal but certainly dramatic.
A.c.contortrix - southern copperhead
The venom contains the disintegrin contortrostatin, a member of the RGD containing platelet aggregation inhibitors specific for the GPIIb/IIIa receptor.
Fibrolase from this venom is a direct-acting nonhemorrhagic fibrinolytic enzyme. This metalloprotease does not belong to the trypsin family of proteases. The venom enzyme cleaves primarily the A alpha-chain of human fibrinogen and fibrin between the Lys-413 and Leu-414 position. The B beta-chain is cleaved more slowly, while the gamma-chain is minimally affected. The cleavage pattern of fibrinogen and fibrin clearly varies from plasmin cleavage of the same molecules. The enzyme does not activate plasminogen or protein c and it is thus different from "Protac", a protein c activator isolated from the same venom.
Agkistrodon contortrix laticinctus (Broad-Banded Copperhead)
ACL hemorrhagic toxin is a fibrinolytic toxin with similar cleavage specificities to other snake venom hemorrhagic toxins, especially fibrolase from A. contortrix contortrix. It has a molecular weight of about 29,000, is slightly acidic, and is a metalloprotease with activity towards the substrates N,N- dimethylcasein and bovine fibrinogen. Although the toxin is able to hydrolyze fibrinogen in vitro, it does not possess any defibrinogenating activity in vivo whereas the crude venom does show this activity.
ACL myotoxin is a basic 14 kDa myonecrotic toxin devoid of phospholipase activity. ACL myotoxin is very similar in mol. wt, amino acid composition, and myotoxic activity to myotoxins isolated from the venoms of Bothrops asper and Porthidium nummifer from Central America, suggesting that homologs of this toxin may be found in other crotaline snake venoms. The venom does also, however, contain myotoxin phospholipase A2s.
Protac is a protein C activator similar to heat stable protein C activators found in Agkistrodon contortrix contortrix, A. c. mokasen, A. c. pictigaster, Agkistrodon piscivorus, A. p. leucostoma and A. bilineatus and less so to the non-heat stable protein C activators found in Bothrops moojeni, B. pradoi, Cerastes cerastes, Vipera lebetina and Daboia russellii venoms. Protac does not exert proteinase activity and is not inhibited by proteinase inhibitors. This component has use as a diagnostic molecule.
A.p.piscivorus (cottonmouth)
Clinical effects - Bites from cottonmouths are severe, with massive local tissue damage and profound disruption of blood chemistry quite similar to that of the crotalids (rattlesnakes).
Applagin is a member of the disintegrin family isolated from this species.
PLA2s have found in A. piscivorus venom. The A. p. piscivorus Asp-49 PLA2 enzyme resembles the Asp-49 enzymes from N. atra and H. haemachatus. In contrast, the A. p. piscivorus Lys-49 PLA2 has much lower enzymatic and anticoagulant activities than the Asp-49 enzymes, but equal cardiotoxic and junctional effects. In contrast to some previous suggestions, basic PLA2 enzymes are not necessarily more toxic than neutral or acidic enzymes.
Piscivorase is a fibrinolytic enzyme. Two isoforms, piscivorase I and II, have been isolated. The mol. wts of these proteases are 23,400 and 29,000 and isoelectric points are 6.6 and 8.5, respectively.. Piscivorase I readily cleaves the A alpha- and B beta-chain of fibrinogen, but piscivorase II cleaves more readily the A alpha-chain and more slowly the B beta-chain. Both fibrinolytic enzymes are also inhibited by cysteine, beta-mercaptoethanol, and by metal chelators such as EDTA and EGTA, but not by benzamidine, phenylmethanesulfonyl fluoride (PMSF), soybean trypsin inhibitor and aprotinin. These fibrinolytic enzymes did not act like thrombin, plasmin and kallikrein, using specific chromogenic substrates. Neither fibrinolytic enzyme induced platelet aggregation, and piscivorase I showed low haemorrhagic activity at dosages of 55 micrograms.