Combining Thiophene-Triazole Hybrids with Bothropic Antivenom to Enhance Its Inhibitory Effect Against the Coagulant Activity of Bothrops Jararaca, B. Neuwiedi, and B. Jararacussu Snake Venoms

INTRODUCTION: Snakebite envenomation causes approximately 5 million incidents, 130,000 deaths, and 400,000 amputations annually worldwide. Thus, the objective of this work was to assess the ability of 16 thiophene-triazole hybrid compounds (6a-6h and 7a-7h) to inhibit the coagulant activity of Bothrops jararaca, B. neuwiedi, and B. jararacussu venoms in combination with commercial antibothropic antivenom. METHOD: In the experimental prevention protocol, human plasma or commercial fibrinogen was incubated for 60 seconds at 37°C with the study compounds, with or without antivenom, followed by the addition of snake venoms. In the treatment protocol, each venom was incubated with plasma or fibrinogens for 60 seconds at 37°C, and then the study compounds, with or without antivenom, were added to the medium. Clotting was monitored using a digital coagulometer. RESULTS: The study compounds inhibited the coagulation of plasma and fibrinogen caused by B. neuwiedi venom under both protocols, but they did not inhibit B. jararacussu venom under the treatment protocol. Overall, the coagulation inhibition was more effective when the study compounds were mixed with antivenom, and some compounds achieved complete prevention of venom- induced coagulation. DISCUSSION: A combination of compounds with antivenom enhanced efficacy in preventing the coagulant activity of Bothrops venoms. CONCLUSION: A drug cocktail comprising the most active compounds mixed with antivenom may be a promising strategy to improve the treatment of envenomation by these snake species.