Native to the Americas, rattlesnakes are pit vipers, a family of vipers with a heat-sensing pit organ between each nostril and eye. Herpetologists first discovered in 1933 that rattlesnakes are immune to their own venom .
Fetuin-A could inhibit metalloproteinases, a class of venom toxins that could cause haemorrhage, damage tissue, and disrupt the coagulation system. By injecting various protein combinations preincubated with C. atrox venom into experimental mice, they found that some combinations successfully blocked haemorrhaging, while some even staved off death. Encouraged by the success of FETUA proteins against C. atrox venom, the team tried them against the eastern diamondback rattlesnake ( Crotalus adamanteus ), which proved successful. Then they tested them against two Asian snakes: the Malayan pit viper ( Calloselasma rhodostoma ) and the Chinese moccasin ( Deinagkistrodon acutus ). The proteins could protect against those as well. “The paper shows convincingly that a combination of naturally evolved FETUA proteins can fully neutralise rattlesnake venom lethality by inhibiting metalloproteinases alone. However, Dr. Sunagar also pointed out that the study did not exactly measure clinical capacity.
In 1972, Japanese researchers discovered the first example of a so-called toxin sponge — a serum protein dubbed Fetuin-A — from Okinawa habu ( Protobothrops flavoviridis ), a pit viper endemic to the Ryukyu Islands. In a new study in Proceedings of the National Academy of Sciences , the team at Maryland has shown that specific combinations of C. atrox FETUA proteins can fully neutralise rattlesnake venom lethality in mice, with roughly 10-times the potency of commercial antivenom. On discovering metalloproteinase-inhibiting FETUA-2, 3, 4, and 5 proteins from C. atrox , the research team studied their antivenom potency.
The test results that followed were a “string of surprises”. The findings are a “real advance” for antivenom development, according to Kartik Sunagar, an associate professor at the Indian Institute of Science, Bengaluru; he was not involved in the study. “Every efficacy experiment premixed venom and inhibitor before injection,” he said. “So the study measures neutralising capacity, not treatment of an animal already envenomed, which is the clinically relevant scenario.”
