A Paradigm Shift in Snakebite Envenoming Therapy: From Conventional Antivenoms to Rationally Designed, Broadly Neutralizing Combination Therapies

For over a century, polyclonal antivenom has been the cornerstone of snakebite therapy, saving countless lives. However, the current production method, based on immunizing large animals, has inherent limitations in terms of safety, stability, and supply reliability, thereby creating a pressing need for alternative technologies. This review charts the rise of next-generation antivenoms built on recombinant antibody engineering. We systematically survey the strategies for discovering and developing these molecules, from humanized monoclonal antibodies and VHHs to computationally designed proteins. Our central thesis is that achieving broad-spectrum neutralization against complex venoms requires a shift from single-agent approaches to rationally designed, oligoclonal “cocktail” therapies (defined mixtures of a few select therapeutic antibodies). Finally, we analyze the critical challenges in bioprocessing, formulation, and regulatory science that must be overcome to translate these promising candidates from the laboratory into globally accessible medicines, and we explore the role of emerging technologies in accelerating this transition.