Possible new antivenom from one of the oldest surviving mammal families

The opossums, or Didelphimorphia, are an order of marsupials found in the Western Hemisphere. They are one of the oldest surviving mammal families, fossil remains of which have been found from 70 million years ago.  Didelphis means double womb and refers to the pouch where infant opossums develop. Although sometimes known as possums they should not be confused with the Australian suborder Phalangeriformes of the same name.

Opossums seem to have a naturally high level of immunity to the venom produced by rattlesnakes, cottonmouths and other pit vipers. The initial studies on this immunity were done in the 1940s and further investigated in the mid-1970s by J A Kilmon, who reported field observations and laboratory trials using Virginia opossums (Didelphis virginiana) and eastern diamondback rattlesnakes (Crotalus adamanteus). Kilmon noted that none of the opossums developed observable local reactions other than trauma attributable to fang penetration and none developed observable systemic effect, exhibiting negligible alteration of heart rate and respiration.

Pit viper venom is haemotoxic but opossums have a blood protein, the von Willebrand Factor (vWF), which improves the animal’s ability to neutralise the anti-coagulant effect of the venom. In the 1990s researchers isolated the peptide from the opossum protein that was responsible for the effect. In a PLoS One article¹ published in 2011, DNA researchers noted a sort of evolutionary arms race whereby the venom gene evolved by rapid mutation while the opossum’s immunity kept pace by unexpectedly high rates of replacement substitutions in the specific amino acids in vWF that interact with toxin proteins.

However, no one seems to have considered the potential of a new antivenom therapy until recently when researchers at San Jose State University synthesized the opossum peptide and found that it protected venom-exposed mice from the bites of US Western Diamondback rattlesnakes (Crotalus atrox) and Russell’s viper (Daboia russelii) from Pakistan. Although the exact mechanism is not known it seems the venom protein binds to the peptide, rendering it no longer toxic. Their work also suggests the antivenom would probably work against venoms from other poisonous snakes, as well as against scorpion, plant and bacterial toxins.

Furthermore the team showed they could program the bacteria Escherichia coli to make the peptide. This technique could enable large quantities of the peptide to be produced inexpensively so making it invaluable to poorer areas of the world where poisonous snakes bite thousands of people every year.

The researchers also reported that tests so far show the peptide purified from E. coli does not produce adverse reactions such as rash, itching, wheezing, rapid heart rate, fever or body aches which are experienced by some patients using antivenoms manufactured by the usual process of injecting the venom into a horse then processing the serum.

Reference:

1 Sharon A. Jansa, Robert S. Voss. Adaptive Evolution of the Venom-Targeted vWF Protein in Opossums that Eat Pitvipers. PLoS ONE, 2011; 6 (6): e20997 DOI: 10.1371/journal.pone.0020997