Integration of transcriptomic profile of SARS-CoV-2 infected normal human bronchial epi-thelial cells with metabolic and protein-protein interaction networks
Integration of transcriptomic profile of SARS-CoV-2 infected normal human bronchial epi-thelial cells with metabolic and protein-protein interaction networks
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DOI：
10.3906/biy-2005-115
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发表时间：
2020-01-01
影响因子：
2.2
通讯作者：
Pir, Pinar
中科院分区：
文献类型：
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作者：
Karakurt, Hamza Umut;Pir, Pinar
一种引起急性呼吸道疾病的新型冠状病毒（SARS-CoV-2，前称nCoV-2019）在中国武汉出现，并于2020年初在全球蔓延。1月30日，世界卫生组织（WHO）宣布这种病毒的传播为流行病和公共卫生紧急情况。由于SARS-CoV-2具有高度传染性和长潜伏期，因此需要采取严格的封锁措施，因此早期诊断至关重要。我们分析了SARS-CoV-2感染的人肺上皮细胞的转录组，并与模拟感染的细胞进行了比较，使用基于网络的报告代谢物方法，并将转录组数据与蛋白质-蛋白质相互作用网络相结合，以阐明早期细胞反应。显著受影响的代谢物具有用于诊断的潜力，而蛋白质簇的途径具有用作支持性或新型治疗方法的靶点的潜力。我们的研究结果与文献中IL 6家族细胞因子的应答及其重要性一致，此外，我们发现基质金属蛋白酶2（MMP 2）和基质金属蛋白酶9（MMP 9）与硫酸角质素合成途径可能在感染中起关键作用。我们假设MMP 9抑制剂有可能预防严重受影响患者的“细胞因子风暴”。
A novel coronavirus (SARS-CoV-2, formerly known as nCoV-2019) that causes an acute respiratory disease has emerged in Wuhan, China and spread globally in early 2020. On January the 30th, the World Health Organization (WHO) declared spread of this virus as an epidemic and a public health emergency. With its highly contagious characteristic and long incubation time, confinement of SARS-CoV-2 requires drastic lock-down measures to be taken and therefore early diagnosis is crucial. We analysed transcriptome of SARS-CoV-2 infected human lung epithelial cells, compared it with mock-infected cells, used network-based reporter metabolite approach and integrated the transcriptome data with protein-protein interaction network to elucidate the early cellular response. Significantly affected metabolites have the potential to be used in diagnostics while pathways of protein clusters have the potential to be used as targets for supportive or novel therapeutic approaches. Our results are in accordance with the literature on response of IL6 family of cytokines and their importance, in addition, we find that matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) with keratan sulfate synthesis pathway may play a key role in the infection. We hypothesize that MMP9 inhibitors have potential to prevent "cytokine storm" in severely affected patients.