Towards better antivenoms: navigating the road to new types of snakebite envenoming therapies

Abstract

Snakebite envenoming is a significant global health challenge, and for over a century, traditional plasma-derived antivenoms from hyperimmunized animals have been the primary treatment against this infliction. However, these antivenoms have several inherent limitations, including the risk of causing adverse reactions when administered to patients, batch-to-batch variation, and high production costs. To address these issues and improve treatment outcomes, the development of new types of antivenoms is crucial. During this development, key aspects such as improved clinical efficacy, enhanced safety profiles, and greater affordability should be in focus. To achieve these goals, modern biotechnological methods can be applied to the discovery and development of therapeutic agents that can neutralize medically important toxins from multiple snake species. This review highlights some of these agents, including monoclonal antibodies, nanobodies, and selected small molecules, that can achieve broad toxin neutralization, have favorable safety profiles, and can be produced on a large scale with standardized manufacturing processes. Considering the inherent strengths and limitations related to the pharmacokinetics of these different agents, a combination of them might be beneficial in the development of new types of antivenom products with improved therapeutic properties. While the implementation of new therapies requires time, it is foreseeable that the application of biotechnological advancements represents a promising trajectory toward the development of improved therapies for snakebite envenoming. As research and development continue to advance, these new products could emerge as the mainstay treatment in the future.

Effect of Seaweed-Derived Fucoidans from Undaria pinnatifida and Fucus vesiculosus on Coagulant, Proteolytic, and Phospholipase A2 Activities of Snake Bothrops jararaca, B. jararacussu, and B. neuwiedi Venom

“…Antivenoms do not neutralize such toxic activities caused by Bothropic venoms [ 41 ] or other vipers [ 42 ] and may even induce hypersensitive reactions in patients [ 14 ]. Thus, molecules able to neutralize the toxic activities of snake venoms are required to improve the recovery of victims of SBE or to prevent sequelae.…”

Improving in vivo assays in snake venom and antivenom research: A community discussion

“…This is further compounded by the development of new generations of envenoming therapeutics which will likely be required to enter through the traditional clinical regulation pathways, and thus will require much more rigorous preclinical in vivo testing and data generation. 64…”

“…These new therapeutic candidates will likely be subjected to appropriate full therapeutic development and regulatory pipelines, being required to proceed through preclinical and clinical assessment before approval. 62,64 Improvements to the standard model: Refinement and Reduction With the above issues in mind, several refinements to the standard neutralisation of lethality assay have been developed in recent times.…”