The Mechanistic Target of Rapamycin (mTOR): Novel Considerations as an Antiviral Treatment.
The Mechanistic Target of Rapamycin (mTOR): Novel Considerations as an Antiviral Treatment.
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DOI：
10.2174/1567202617666200425205122
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发表时间：
2020
影响因子：
2.1
通讯作者：
Maiese K
中科院分区：
文献类型：
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作者：
Maiese K
多种病毒病原体可对个人造成重大健康风险。最近的一个例子是，β-冠状病毒家族病毒粒子SARS-CoV-2迅速演变为导致2019冠状病毒病（COVID-19）的大流行，并已被世界卫生组织宣布为国际关注的突发公共卫生事件。迄今为止，没有针对COVID-19的明确治疗方法或疫苗应用。尽管新的研究试图重新利用现有的COVID-19抗病毒治疗方法，但通常不被认为具有抗病毒能力的创新治疗策略可能对解决这一全球关切至关重要。其中一种可能被证明是非常富有成效的，并提供令人兴奋的新抗病毒治疗潜力的途径涉及雷帕霉素（mTOR）的机制靶点及其相关的mTOR复合物1 (mTORC1)， mTOR复合物2 （mTORC2）和AMP激活的蛋白激酶（AMPK）。最近的研究表明，mTOR通路与AMPK结合可能为控制细胞损伤、氧化应激、线粒体功能障碍和高炎症的发作提供了有价值的靶点，高炎症是与COVID-19相关的一种重要残疾。此外，可以激活mTOR的途径可能是抗丙型肝炎活性、减少甲型流感病毒复制所必需的，并且对于流感疫苗接种的1型干扰素应答至关重要。然而，开发安全有效的mTOR途径抗病毒治疗的重要考虑是存在的。在某些条件下，mTOR可以作为一把双刃剑，参与病毒粒子的复制和从细胞中释放病毒粒子。未来将mTOR作为潜在抗病毒靶点的研究是非常必要的，随着对这一新途径的更深入了解，针对几种病毒病原体的新治疗方法可能会成功出现。
Multiple viral pathogens can pose a significant health risk to individuals. As a recent example, the β-coronavirus family virion, SARS-CoV-2, has quickly evolved as a pandemic leading to coronavirus disease 2019 (COVID-19) and has been declared by the World Health Organization as a Public Health Emergency of International Concern. To date, no definitive treatment or vaccine application exists for COVID-19. Although new investigations seek to repurpose existing antiviral treatments for COVID-19, innovative treatment strategies not normally considered to have antiviral capabilities may be critical to address this global concern. One such avenue that may prove to be exceedingly fruitful and offer exciting potential as new antiviral therapy involves the mechanistic target of rapamycin (mTOR) and its associated pathways of mTOR Complex 1 (mTORC1), mTOR Complex 2 (mTORC2), and AMP activated protein kinase (AMPK). Recent work has shown that mTOR pathways in conjunction with AMPK may offer valuable targets to control cell injury, oxidative stress, mitochondrial dysfunction, and the onset of hyperinflammation, a significant disability associated with COVID-19. Furthermore, pathways that can activate mTOR may be necessary for anti-hepatitis C activity, reduction of influenza A virus replication, and vital for type-1 interferon responses with influenza vaccination. Yet, important considerations for the development of safe and effective antiviral therapy with mTOR pathways exist. Under some conditions, mTOR can act as a double edge sword and participate in virion replication and virion release from cells. Future work with mTOR as a potential antiviral target is highly warranted and with a greater understanding of this novel pathway, new treatments against several viral pathogens may successfully emerge.