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变纹矛头蝮蛇毒蛋白质的蛇毒组学及F(ab')₂抗蛇毒组学研究

Venomic and F(ab')₂ antivenomic studies of Bothrops alternatus venom proteins.

作者信息

Fusco Luciano S, Beraldo-Neto Emidio, Calvete Juan J, Sanz Libia, Lanari Laura C, Lorente Carolina, Leiva Laura C, Pimenta Daniel, de Roodt Adolfo R, Pla Davinia

机构信息

Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Química Básica y Aplicada del Nordeste Argentino (IQUIBA-NEA), Corrientes, Argentina; Facultad de Ciencias Exactas y Naturales y Agrimensura, Universidad Nacional del Nordeste (UNNE), Avenida Libertad 5470, 3400 Corrientes, Argentina.

Laboratorio de Bioquímica y Biofísica, Instituto Butantan, São Paulo, SP, Brazil.

出版信息

Int J Biol Macromol. 2025 Jul;318(Pt 2):144777. doi: 10.1016/j.ijbiomac.2025.144777. Epub 2025 May 30.

DOI:10.1016/j.ijbiomac.2025.144777
PMID:40451370
Abstract

In this study, using a proteomic approach, we performed the venomic characterization of B. alternatus venom proteins. The venom comprises toxins from eleven protein families and the main identified included PIII-SVMP (27.32%), PII-SVMP (12.33%), Disintegrin-SVMP (10.26%), SVSP (8.80%), PLA2 (6.85%), BBP/C-NP (4.85%), CRVP (4.87%), CTL (6.80%), LAAO (4.14%), SVGF (1.90%), VPA (1.64%), PDE (0.07%), and an unidentified percentage (11.64%). Antivenomic analysis showed that both F(ab')₂ antivenoms recognized all venom proteins but had low affinity for small peptides like BPP. The BIOL antivenom demonstrated a binding capacity of 56.92 mg/g F(ab')2, while the INPB antivenom showed a significantly higher binding capacity of 124.78 mg/g F(ab')2. These results align with in vivo studies, where the antivenom potency was 63.28 mg/g F(ab')2 and 129.38 mg/g F(ab')2 for BIOL and INPB, respectively. This study highlights the value of third-generation antivenomics in characterizing antivenoms used against B. alternatus envenomation and confirms the effectiveness of these two antivenoms in treating snakebites caused by B. alternatus. In conclusion, this study reports for the first time a comparative analysis of the venomics and antivenomics of two antivenoms used in Argentina for the treatment of B. alternatus snake bites, integrating both in vitro and in vivo approaches.

摘要

在本研究中,我们采用蛋白质组学方法对松材线虫毒液蛋白进行了毒液组学表征。该毒液包含来自11个蛋白家族的毒素,主要鉴定出的成分包括PIII-SVMP(27.32%)、PII-SVMP(12.33%)、解整合素-SVMP(10.26%)、SVSP(8.80%)、PLA2(6.85%)、BBP/C-NP(4.85%)、CRVP(4.87%)、CTL(6.80%)、LAAO(4.14%)、SVGF(1.90%)、VPA(1.64%)、PDE(0.07%)以及未鉴定比例(11.64%)。抗毒液组学分析表明,两种F(ab')₂抗蛇毒血清均能识别所有毒液蛋白,但对BPP等小肽的亲和力较低。BIOL抗蛇毒血清的结合能力为56.92 mg/g F(ab')2,而INPB抗蛇毒血清的结合能力显著更高,为124.78 mg/g F(ab')2。这些结果与体内研究结果一致,在体内研究中,BIOL和INPB抗蛇毒血清的抗毒效力分别为63.28 mg/g F(ab')2和129.38 mg/g F(ab')2。本研究突出了第三代抗毒液组学在表征用于治疗松材线虫中毒的抗蛇毒血清方面的价值,并证实了这两种抗蛇毒血清在治疗松材线虫引起的蛇咬伤方面的有效性。总之,本研究首次报告了阿根廷用于治疗松材线虫蛇咬伤的两种抗蛇毒血清的毒液组学和抗毒液组学的比较分析,整合了体外和体内方法。

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