Department of Pharmacology, Vascular Biology and Therapeutic Program, Yale School of Medicine, New Haven, CT; and.
Department of Comparative Medicine, School of Medicine, Yale University, New Haven, CT.
J Immunol. 2022 Aug 15;209(4):723-730. doi: 10.4049/jimmunol.2100968. Epub 2022 Aug 1.
Severe acute respiratory syndrome coronavirus 2, responsible for the severe acute respiratory syndrome known as COVID-19, has rapidly spread in almost every country and devastated the global economy and health care system. Lung injury is an early disease manifestation believed to be a major contributor to short- and long-term pathological consequences of COVID-19, and thus drug discovery aiming to ameliorate lung injury could be a potential strategy to treat COVID-19 patients. By inducing a severe acute respiratory syndrome-like pulmonary disease model through infecting A/J mice with murine hepatitis virus strain 1 (MHV-1), we show that i.v. administration of pazopanib ameliorates acute lung injuries without affecting MHV-1 replication. Pazopanib reduces cell apoptosis in MHV-1-infected lungs. Furthermore, we also identified that pazopanib has to be given no later than 48 h after the virus infection without compromising the therapeutic effect. Our study provides a potential treatment for coronavirus-induced lung injuries and support for further evaluation of pazopanib in COVID-19 patients.
严重急性呼吸综合征冠状病毒 2 型(SARS-CoV-2)是导致严重急性呼吸综合征(COVID-19)的病原体,它已在几乎所有国家迅速传播,严重破坏了全球经济和医疗保健系统。肺损伤是 COVID-19 的早期疾病表现,被认为是导致 COVID-19 患者短期和长期病理后果的主要因素之一,因此,旨在改善肺损伤的药物发现可能是治疗 COVID-19 患者的潜在策略。通过用鼠肝炎病毒 1 株(MHV-1)感染 A/J 小鼠来诱导类似于严重急性呼吸综合征的肺部疾病模型,我们发现静脉内给予帕唑帕尼可改善急性肺损伤,而不影响 MHV-1 的复制。帕唑帕尼可减少 MHV-1 感染肺中的细胞凋亡。此外,我们还发现帕唑帕尼必须在病毒感染后 48 小时内给予,而不影响治疗效果。我们的研究为冠状病毒引起的肺损伤提供了一种潜在的治疗方法,并支持进一步评估帕唑帕尼在 COVID-19 患者中的应用。