Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) is associated with uncontrolled inflammatory responses. Loss of pulmonary angiotensin-converting enzyme 2 (ACE2) function has been associated with SARS-CoV-2 infection. The aberrant signalling and dysregulated inflammation characteristic of lung cancer have marked similarities with SARS-CoV-2 infection. Spearman’s correlation analysis of The Cancer Genome Atlas (TCGA) datasets indicated an inverse correlation between ACE2 and IL6 in lung adenocarcinoma. qRT-PCR analysis revealed CoV-2-SRBD-mediated diminished ACE2 expression in lung cancer cells that was concomitant with increased IL6 expression. Western blot and qRT-PCR analysis suggested that treatment with methotrexate (MTx) dampened CoV-2-SRBD-mediated increase in JAK1/STAT3 phosphorylation, gp130, IL6, and folate-binding protein (FBP) expressions. MTx also rescued the diminished expression of ACE2 in CoV-2-SRBD transfected cells. As lung tissue injury in severely affected COVID-19 patients is characterised by aberrant inflammatory response, repurposing MTx as an effective therapy against critical regulators of inflammation in SARS-CoV-2 infection warrants investigation.

严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 感染 (COVID-19) 与不受控制的炎症反应有关。肺血管紧张素转换酶 2 (ACE2) 功能的丧失与 SARS-CoV-2 感染有关。肺癌的异常信号传导和失调的炎症特征与 SARS-CoV-2 感染有明显的相似之处。Spearman 对癌症基因组图谱 (TCGA) 数据集的相关性分析表明，肺腺癌中ACE2和IL6之间存在负相关。qRT-PCR 分析显示 CoV-2-SRBD 介导的肺癌细胞中ACE2表达减少，伴随着IL6增加表达。蛋白质印迹和 qRT-PCR 分析表明，甲氨蝶呤 (MTx) 治疗抑制了 CoV-2-SRBD 介导的 JAK1/STAT3 磷酸化、gp130、IL6 和叶酸结合蛋白 (FBP) 表达的增加。MTx 还挽救了CoV-2-SRBD 转染细胞中ACE2表达减少的情况。由于受严重影响的 COVID-19 患者的肺组织损伤以异常炎症反应为特征，因此将 MTx 重新用作针对 SARS-CoV-2 感染中炎症关键调节因子的有效疗法值得研究。