Comprehensive Analysis of Conserved B-Cell Epitopes in DENV NS1 Protein for Enhanced Rapid Diagnostic Tests Development in Indonesia

Y. Messe, S. Wibowo, Hery Wijayanto, W. Artama, Fajar Sofyantoro, Nastiti Wijayanti
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Abstract

Dengue virus (DENV) constitutes a formidable public health threat within tropical and subtropical regions. The escalation of cases in Southeast Asia, notably Indonesia, is a matter of considerable concern. Timely identification of DENV infection remains imperative for efficient disease management. The non-structural protein-1 (NS1), distinguished by its heightened immunogenicity and early detectability during infection, stands as a pivotal target for diagnostic modalities. The current investigation delves into the exploration of B-cell epitopes within Indonesian DENV NS1 protein isolates, with the overarching objective of enhancing the sensitivity and specificity of early detection systems, such as the Rapid Diagnostic Test (RDT). This study has successfully delineated five B-cell epitopes that exhibit conservation across DENV serotypes within Indonesian isolates (accessions number: QBB90021.1, QBE90252.1, QBB90023.1, and UDW38833.1). These epitopes were discerned through comprehensive screening leveraging the IEDB platforms. Noteworthy variations in antigenicity, allergenicity, and toxicity profiles were observed among these identified epitopes. Molecular docking analysis substantiated a robust binding affinity between the predicted epitope and the B-cell receptor. The ensuing in silico protein-peptide docking analyses offer valuable insights into potential B-cell epitopes on the Indonesian DENV NS1 protein. The identified epitopes, particularly the SQHNYRPGY epitope characterized by its antigenic potency and non-allergenic attributes, hold promise for advancing the development of sensitive and specific RDTs tailored for DENV detection in the Indonesian context. However, it is imperative to underscore the requisite for subsequent experimental validation to affirm the efficacy of these epitopes in diagnostic applications.
全面分析印度尼西亚用于强化快速诊断检测开发的 DENV NS1 蛋白中的保守 B 细胞表位
登革热病毒(DENV)对热带和亚热带地区的公共卫生构成严重威胁。东南亚,尤其是印度尼西亚的病例不断增加,令人十分担忧。及时发现 DENV 感染是有效控制疾病的当务之急。非结构蛋白-1(NS1)具有较强的免疫原性,在感染期间可被早期检测到,是诊断方法的关键目标。目前的调查深入探讨了印度尼西亚 DENV NS1 蛋白分离物中的 B 细胞表位,其总体目标是提高快速诊断检测(RDT)等早期检测系统的灵敏度和特异性。这项研究成功地界定了印度尼西亚分离物中不同 DENV 血清型的五个 B 细胞表位(登录号:QBB90021.1、QBE90252.1、QBB90023.1 和 UDW38833.1)。这些表位是通过利用 IEDB 平台进行全面筛选而确定的。在这些已确定的表位中观察到了抗原性、过敏性和毒性方面的显著差异。分子对接分析证实,预测的表位与 B 细胞受体之间有很强的结合亲和力。随后进行的硅学蛋白-肽对接分析为了解印度尼西亚 DENV NS1 蛋白上潜在的 B 细胞表位提供了宝贵的信息。已确定的表位,尤其是以抗原效力和非过敏属性为特征的 SQHNYRPGY 表位,有望推动开发灵敏、特异的 RDTs,用于印度尼西亚的 DENV 检测。不过,必须强调的是,必须进行后续实验验证,以确认这些表位在诊断应用中的有效性。
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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