The project focuses on developing a revolutionary generation of universal snakebite antidotes, answering an urgent WHO health priority.
Snakebite envenoming is the deadliest neglected tropical disease. Over five million snakebites annually cause up to 138 thousand deaths and 400 thousand of permanent disabilities and amputations. Unfortunately, the current antibody-based therapy is too expensive for the poor rural communities most affected by snakebites, snake-specific and plagued by anaphylactic reactions.
We aim to develop a new cheap and safe antidote with broad snake-species efficiency targeting critical venom toxins to overcome the devastating consequences of envenomation.
For that purpose, we will determine the reaction mechanisms of two principal venom enzymes, PLA2 and HYA, with DFT/MM MD methods and use the transition states as templates for discovering toxin inhibitors within databases of druglike compounds.
The best candidate molecules will be tested in vivo by world leaders in snake venom biochemistry and constitute the basis for the revolutionary universal, and affordable antidote. DFT/MM MD and cMD are extremely CPU-intensive (millions of core hours) and highly scalable (hundreds of CPU cores) they cannot be performed in local clusters but are ideally suited for high-performance computing.