Ain Qurrat Ul, Sufyan Muhammad, Mufti Isra Umbreen, Shahid Imran, Alzahrani Abdullah R, Rehman Sidra
Department of Biosciences, COMSATS University Islamabad (CUI), Park Road, Islamabad, 45550, Pakistan; Department of Medical Laboratory Technology, The Islamia University of Bahawalpur, Bahawalpur, 63100, Pakistan.
Department of Bioinformatics and Biotechnology, Government College University Faisalabad, Faisalabad, 38000, Pakistan.
Microb Pathog. 2025 Oct;207:107885. doi: 10.1016/j.micpath.2025.107885. Epub 2025 Jul 9.
Dengue infection is one of the most widely spread flavivirus infections. Despite the fatality it could cause, no antiviral treatment is currently available to treat the disease and its associated pathophysiological conditions. This study aimed to search drug-like compounds for possible inhibitors of the NS5 protein of dengue virus (serotype 2). In the present study, a data set of twenty-five Beta vulgaris. L-based phytoconstituents was developed. We employed machine learning (ML) data pre-processing, screening of differentially expressed transcripts and genes, identification of common transcriptional signatures and pathways and function enrichment analysis of dengue infection; and protein-protein interaction network construction and identification of hub genes. ML data revealed that NS5 mRNA was downregulated by betanin, kaempferol, quercetin hydrate, and isovitexin-2-O-xyloside. Moreover, administering these compounds can alleviate host innate immune factor suppression mediated by NS5, thereby exhibiting antiviral activity. Molecular docking and pharmacokinetics studies revealed a potential therapeutic role of betanin, kaempferol, quercetin hydrate, and isovitexin-2-O-xyloside phytoconstituents as potent antiviral phytocompounds. MD simulation and post-simulation analysis, including principal component analysis and dynamic cross-correlation, confirmed the antiviral therapeutic potency of betanin, kaempferol, and isovitexin-2-O-xyloside against dengue virus infection. In vitro cytotoxic studies also depicted nontoxic effects of betanin and quercetin hydrate in Vero and CHO cells at a concentration range of 20-0.31 μM. In summary, computational screening and in vitro cytotoxicity analysis revealed that betanin, kaempferol, and isovitexin-2-O-xyloside may prove as potential drug candidates against dengue virus regarding their possible safety and antiviral activity in future.
登革热感染是传播最广泛的黄病毒感染之一。尽管它可能导致死亡，但目前尚无抗病毒治疗方法来治疗该疾病及其相关的病理生理状况。本研究旨在寻找可能抑制登革病毒（血清型2）NS5蛋白的类药物化合物。在本研究中，建立了一个包含25种甜菜根属植物成分的数据集。我们采用机器学习（ML）数据预处理、差异表达转录本和基因筛选、登革热感染常见转录特征和途径的鉴定以及功能富集分析；构建蛋白质-蛋白质相互作用网络并鉴定枢纽基因。ML数据显示，甜菜红素、山奈酚、水合槲皮素和异荭草素-2-O-木糖苷可下调NS5 mRNA。此外，施用这些化合物可减轻NS5介导的宿主先天免疫因子抑制，从而表现出抗病毒活性。分子对接和药代动力学研究揭示了甜菜红素、山奈酚、水合槲皮素和异荭草素-2-O-木糖苷植物成分作为有效的抗病毒植物化合物的潜在治疗作用。分子动力学（MD）模拟和模拟后分析，包括主成分分析和动态交叉相关性分析，证实了甜菜红素、山奈酚和异荭草素-2-O-木糖苷对登革病毒感染的抗病毒治疗效力。体外细胞毒性研究还表明，在20-0.31μM的浓度范围内，甜菜红素和水合槲皮素对Vero细胞和CHO细胞无毒性作用。总之，计算筛选和体外细胞毒性分析表明，甜菜红素、山奈酚和异荭草素-2-O-木糖苷因其未来可能的安全性和抗病毒活性，可能被证明是抗登革病毒的潜在候选药物。
