Palakkott Abdul Rasheed, Alneyadi Aysha, Muhammad Khalid, Eid Ali Hussein, Amiri Khaled M A, Akli Ayoub Mohammed, Iratni Rabah
Department of Biology, College of Science, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates.
Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, Qatar.
Vaccines (Basel). 2023 Mar 30;11(4):768. doi: 10.3390/vaccines11040768.
The coronavirus disease-19 (COVID-19) pandemic is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). At the molecular and cellular levels, the SARS-CoV-2 uses its envelope glycoprotein, the spike S protein, to infect the target cells in the lungs via binding with their transmembrane receptor, the angiotensin-converting enzyme 2 (ACE2). Here, we wanted to investigate if other molecular targets and pathways may be used by SARS-CoV-2. We investigated the possibility of the spike 1 S protein and its receptor-binding domain (RBD) to target the epidermal growth factor receptor (EGFR) and its downstream signaling pathway in vitro using the lung cancer cell line (A549 cells). Protein expression and phosphorylation were examined upon cell treatment with the recombinant full spike 1 S protein or RBD. We demonstrate for the first time the activation of EGFR by the Spike 1 protein associated with the phosphorylation of the canonical Extracellular signal-regulated kinase1/2 (ERK1/2) and AKT kinases and an increase in survivin expression controlling the survival pathway. Our study suggests the putative implication of EGFR and its related signaling pathways in SARS-CoV-2 infectivity and COVID-19 pathology. This may open new perspectives in the treatment of COVID-19 patients by targeting EGFR.
新型冠状病毒肺炎（COVID-19）大流行是由新型严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起的。在分子和细胞水平上，SARS-CoV-2利用其包膜糖蛋白刺突S蛋白，通过与跨膜受体血管紧张素转换酶2（ACE2）结合来感染肺部的靶细胞。在此，我们想研究SARS-CoV-2是否可能利用其他分子靶点和途径。我们使用肺癌细胞系（A549细胞）在体外研究了刺突1 S蛋白及其受体结合域（RBD）靶向表皮生长因子受体（EGFR）及其下游信号通路的可能性。在用重组全长刺突1 S蛋白或RBD处理细胞后，检测蛋白质表达和磷酸化情况。我们首次证明了刺突1蛋白激活EGFR，这与经典的细胞外信号调节激酶1/2（ERK1/2）和AKT激酶的磷酸化以及控制生存途径的生存素表达增加有关。我们的研究表明EGFR及其相关信号通路可能参与SARS-CoV-2的感染性和COVID-19的病理过程。这可能为通过靶向EGFR治疗COVID-19患者开辟新的前景。
