Development of peptide inhibitors against functional components of snake venom; a new approach
Envenomation resulting from snake bite is a significant problem faced by both developed and developing countries. Within South Asia, India is quite heavily affected with an estimated 46,000 deaths per year. Currently available anti-venom therapy consists of polyvalent immunoglobulin fractions prepared from the plasma of donor animals, typically horses or sheep that were immunized with a mixture of venoms from different snake species. This is often problematic, as the non-human immunoglobulins may cause severe immune reactions. Additionally, due to significant regional variation of venom composition, these anti-venoms may only be effective against envenomation by snakes displaying a similar profile of venom composition as the venom sources used for immunization.
To address the issues of immune reactions and batch variation associated with conventional anti-venom, we decided to utilize protein protein interaction screens (eg phage display) to develop peptides that can neutralize relevant toxic venom components with high specificity. Component specific inhibitors or neutralizing agents should have the advantage that they can be produced and combined in a controlled fashion such that all venom components are covered and neutralized effectively. We seek to avoid harmful immune reactions by fusing inhibitory peptides with suitable scaffold proteins, such as human antibody fragments.