V-ToCs(毒液毒素聚类):蛇毒毒素序列和结构相似性研究工具。

IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Toxicon Pub Date : 2024-08-31 DOI:10.1016/j.toxicon.2024.108088
Konstantinos Kalogeropoulos , Vlad Rosca , Carol O'Brien , Charlotte Risager Christensen , Rahmat Grahadi , Christoffer Vinther Sørensen , Max D. Overath , Diego Ruiz Espi , David E. Jenkins , Ulrich auf dem Keller , Andreas H. Laustsen , Thomas J. Fryer , Timothy P. Jenkins
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引用次数: 0

摘要

最近,人们大力推动开发下一代抗蛇咬伤疗法。然而,与目前依赖动物多克隆抗体的抗蛇毒血清不同,这些新方法大多依赖于对 2000 多种已知蛇毒毒素的深入了解。事实上,通过识别这些不同毒素的相似性(即保守表位),就有可能设计出针对这些相似性的交叉反应疗法,如广谱中和抗体。因此,在本项目中,我们建立了一个自动管道,可生成所有可用蛇毒毒素序列和结构的序列和结构距离矩阵及同源性树。为便于分析,我们还开发了一种用户友好型高通量可视化工具,即 "毒液毒素聚类"(V-ToCs)。研究人员可以利用该工具轻松研究 SVT 的序列和结构模式,以实现阐明毒素进化等多种目的,并有望在不久的将来为发现和开发具有更广泛中和作用的抗蛇毒血清提供指导。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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V-ToCs (Venom Toxin Clustering): A tool for the investigation of sequence and structure similarities in snake venom toxins

Recently, there has been a major push toward the development of next-generation treatments against snakebite envenoming. However, unlike current antivenoms that rely on animal-derived polyclonal antibodies, most of these novel approaches are reliant on an in-depth understanding of the over 2000 known snake venom toxins. Indeed, by identifying similarities (i.e., conserved epitopes) across these different toxins, it is possible to design cross-reactive treatments, such as broadly-neutralising antibodies, that target these similarities. Therefore, in this project, we built an automated pipeline that generates sequence and structural distance matrices and homology trees across all available snake venom toxin sequences and structures. To facilitate analysis, we also developed a user-friendly and high-throughput visualisation tool, coined “Venom TOxin CluStering” (V-ToCs). This tool allows researchers to easily investigate sequence and structure patterns in snake venom toxins for a wide array of purposes, such as elucidating toxin evolution, and will also hopefully help guide the discovery and development of increasingly broadly-neutralising antivenoms in the near future.

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来源期刊
Toxicon
Toxicon 医学-毒理学
CiteScore
4.80
自引率
10.70%
发文量
358
审稿时长
68 days
期刊介绍: Toxicon has an open access mirror Toxicon: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. An introductory offer Toxicon: X - full waiver of the Open Access fee. Toxicon''s "aims and scope" are to publish: -articles containing the results of original research on problems related to toxins derived from animals, plants and microorganisms -papers on novel findings related to the chemical, pharmacological, toxicological, and immunological properties of natural toxins -molecular biological studies of toxins and other genes from poisonous and venomous organisms that advance understanding of the role or function of toxins -clinical observations on poisoning and envenoming where a new therapeutic principle has been proposed or a decidedly superior clinical result has been obtained. -material on the use of toxins as tools in studying biological processes and material on subjects related to venom and antivenom problems. -articles on the translational application of toxins, for example as drugs and insecticides -epidemiological studies on envenoming or poisoning, so long as they highlight a previously unrecognised medical problem or provide insight into the prevention or medical treatment of envenoming or poisoning. Retrospective surveys of hospital records, especially those lacking species identification, will not be considered for publication. Properly designed prospective community-based surveys are strongly encouraged. -articles describing well-known activities of venoms, such as antibacterial, anticancer, and analgesic activities of arachnid venoms, without any attempt to define the mechanism of action or purify the active component, will not be considered for publication in Toxicon. -review articles on problems related to toxinology. To encourage the exchange of ideas, sections of the journal may be devoted to Short Communications, Letters to the Editor and activities of the affiliated societies.
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