Exploration of the effect of protease inhibitor activity on snake venoms

Abstract

Envenomation by snakes is a worldwide health crisis. Anti-venom, the current treatment standard, is a costly and imperfect treatment. Without proper ID of the snake species, the treatment provider is guessing at which anti-venom to use. Many snakes are also able to control venom release as they age, so not every bite by a venomous snake is envenoming. Treatment by anti-venom has the potential of severe side effects so treating a snake bite that hasn't resulted in envenoming could cause more problems than withholding treatment. Can protease inhibitors be used to block or decrease the gelatinase activity of snake venom? Established baseline venom activity and dose dependence of inhibition. Activity was measured with a fluorescein-labeled gelatin. NNGH is the enzyme inhibitor that was used. In dose-response experiments, there is significant gelatinase activity and over 50% inhibition by NNGH in Agkistrodon contortrix and complete inhibition in Crotalus atrox. We also see 50% inhibition of Cerastes cerastes venom by NNGH but the species has near half the initial gelatinase activity of C. atrox. These results provide substantial support that venoms of Crotalinae species, pit vipers, are inhibited by the protease inhibitor NNGH, supporting future research endeavors

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