Spider venom peptides Ht1a and Gg1a are toxic to honeybee parasite Varroa destructor by topical application

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  Spider venom peptides Ht1a and Gg1a are toxic to honeybee parasite Varroa destructor by topical application Abstract Global food supply strongly depends on honeybee pollination services, which are threatened by insecticides and pests such as parasitic Varroa destructor mites. Chemical varroacides/acaricides are hampered by resistance development, necessitating the development of sustainable and environmentally friendly alternatives, with arthropod venom peptides being considered promising sources of acaricidal toxins. With only a few acaricidal venom peptides being reported, we performed a systematic topical screening of 50 arthropod venoms against V. destructor , with 78% of the venoms causing 100% mortality after 24 h. Deconvolution of the venoms from the Tasmanian cave spider Hickmania troglodytes and the Giant Japanese funnel-web spider Gigathele gigas led to identification of the varroacidal peptides Ht1a and Gg1a. Topical application of Ht1a and Gg1a reduced varroa mite ...

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