Proteomic characterization of Tityus championi venom and recombinant expression of its major neurotoxin

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  Proteomic characterization of Tityus championi venom and recombinant expression of its major neurotoxin Abstract Background:   Tityus championi is a species endemic to the southern Talamanca Mountain Range, along the border region between Costa Rica and Panama, and has been associated with severe clinical cases. Despite its medical relevance, the composition of its venom remains poorly studied. The present study aimed to characterize the proteomic composition of T. championi venom, identify its main toxin families, and recombinantly produce one of its most abundant and lethal toxins for potential use in antivenom development. Methods:   Venom composition was analyzed by tandem mass spectrometry (MS/MS), enabling the identification of venom proteins. Subsequently, one of its primary lethal toxins (Tcham27) was identified and recombinantly expressed. Results:   Proteomic analysis revealed that the most abundant family in the venom corresponded to metalloproteases, ...

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

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

Abstract

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.

A Paradigm Shift in Snakebite Envenoming Therapy: From Conventional Antivenoms to Rationally Designed, Broadly Neutralizing Combination Therapies
Ning Shi, Jie Wang, Can Xu, Xingjun Jiang, Caiping Ren, Xiang Gao, and Longlong Luo
ACS Pharmacology & Translational Science Article ASAP
DOI: 10.1021/acsptsci.6c00130