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Neurotoxic targeting by elapid snakes dominates the literature in this regard; however, recent studies have revealed viper toxins also induce neurotoxic effect. While this effect is thought to primarily be driven by prey selectivity, no study has quantified the taxonomically specific neurotoxicity of the viper clade consisting of <jats:italic>Daboia<\/jats:italic>, <jats:italic>Macrovipera<\/jats:italic>, <jats:italic>Montivipera<\/jats:italic>, and <jats:italic>Vipera<\/jats:italic> genera. Here, we tested venom toxin binding from 28 species of vipers from the four genera on the alpha 1 neuronal nicotinic acetylcholine receptors (nAChRs) orthosteric sites of amphibian, avian, lizard, rodent, and human mimotopes (synthetic peptides) using the Octet HTX biolayer interferometry platform. <jats:italic>Daboia siamensis<\/jats:italic> and <jats:italic>D. russelii<\/jats:italic> had broad binding affinity towards all mimotopes, while <jats:italic>D. palestinae<\/jats:italic> had selectivity toward lizard. <jats:italic>Macrovipera<\/jats:italic> species, on the other hand, were observed to have a higher affinity for amphibian mimotopes except for <jats:italic>M. schweizeri<\/jats:italic>, which inclined more toward lizard mimotopes. All <jats:italic>Montivipera<\/jats:italic> and most <jats:italic>Vipera<\/jats:italic> species also had higher affinity toward lizard mimotopes. <jats:italic>Vipera a. montandoni<\/jats:italic>, <jats:italic>V. latastei<\/jats:italic>, <jats:italic>V. nikolski<\/jats:italic>, and <jats:italic>V. transcaucasina<\/jats:italic> had the least binding to any of the mimotopes of the study. While a wide range of affinity binding towards various mimotopes were observed within the clade, the lowest affinity occurred towards the human target. <jats:italic>Daboia siamensis<\/jats:italic> and <jats:italic>Macrovipera lebetina<\/jats:italic> exhibited the greatest affinity toward the human mimotope, albeit still the least targeted of the mimotopes within those species. Overlaying this toxin-targeting trait over phylogeny of this clade revealed multiple cases of amplification of this trait and several cases of secondary loss. Overall, our results reveal dynamic variation, amplification, and some secondary loss of the prey targeting trait by alpha-neurotoxins within the venoms of this clade, indicating evolutionary selection pressure shaping the basic biochemistry of these venoms. Our work illustrates the successful use of this biophysical assay to further research snake venom neurotoxins and emphasizes the risk of generalizing venom effects observed on laboratory animals to have similar effects on humans.\n<\/jats:p>","DOI":"10.1007\/s12640-022-00572-w","type":"journal-article","created":{"date-parts":[[2022,10,4]],"date-time":"2022-10-04T10:03:33Z","timestamp":1664877813000},"page":"1793-1801","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Diverse and Dynamic Alpha-Neurotoxicity Within Venoms from the Palearctic Viperid Snake Clade of Daboia, Macrovipera, Montivipera, and Vipera"],"prefix":"10.1007","volume":"40","author":[{"given":"Abhinandan","family":"Chowdhury","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina N.","family":"Zdenek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bryan G.","family":"Fry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,10,4]]},"reference":[{"key":"572_CR1","unstructured":"Boyer L, Alag\u00f3n A, Fry BG, Jackson TNW, K. 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