1Institute of Biodiversity and Ecosystem Research, Bulgarian Academy of Science, Sofia 1113, Bulgaria.
Pharmacognosy Research Laboratories and Herbal Analysis Services, School of Science, University of Greenwich, Central Avenue, Chatham-Maritime, Kent ME4 4TB, United Kingdom.
Comb Chem High Throughput Screen. 2022;25(11):1805-1808. doi: 10.2174/1386207325666211130140923.
Infection by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) provokes acute inflammation due to extensive replication of the virus in the epithelial cells of the upper and lower respiratory system. The mammalian target of rapamycin (mTOR) is a l signalling protein with critical functions in cell growth, metabolism, and proliferation. It is known for its regulatory functions in protein synthesis and angiogenesis cascades. The structure of mTOR consists of two distinct complexes (mTORC1 and mTORC2) with diverse functions at different levels of the signalling pathway. By activating mRNA translation, the mTORC1 plays a key role in regulating protein synthesis and cellular growth. On the other hand, the functions of mTORC2 are mainly associated with cell proliferation and survival. By using an appropriate inhibitor at the right time, mTOR modulation could provide immunosuppressive opportunities as antirejection regimens in organ transplantation as well as in the treatment of autoimmune diseases and solid tumours. The mTOR also has an important role in the inflammatory process. Inhibitors of mTOR might indeed be promising agents in the treatment of viral infections. They have further been successfully used in patients with severe influenza A/H1N1 pneumonia and acute respiratory failure. The officially accepted mTOR inhibitors that have undergone clinical testing are sirolimus, everolimus, temsirolimus, and tacrolimus. Thus, further studies on mTOR inhibitors for SARS-CoV-2 infection or COVID-19 therapy are well merited.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染会引发急性炎症，因为病毒在上呼吸道和下呼吸道的上皮细胞中广泛复制。哺乳动物雷帕霉素靶蛋白（mTOR）是一种信号蛋白，在细胞生长、代谢和增殖中具有关键功能。它以其在蛋白质合成和血管生成级联中的调节功能而闻名。mTOR 的结构由两个不同的复合物（mTORC1 和 mTORC2）组成，在信号通路的不同水平具有不同的功能。mTORC1 通过激活 mRNA 翻译，在调节蛋白质合成和细胞生长方面发挥关键作用。另一方面，mTORC2 的功能主要与细胞增殖和存活有关。通过在适当的时间使用适当的抑制剂，mTOR 调节可能为器官移植中的抗排斥方案以及自身免疫性疾病和实体瘤的治疗提供免疫抑制机会。mTOR 在炎症过程中也具有重要作用。mTOR 抑制剂实际上可能是治疗病毒感染的有前途的药物。它们已成功用于治疗严重甲型流感 A/H1N1 肺炎和急性呼吸衰竭的患者。经过临床测试的官方认可的 mTOR 抑制剂有西罗莫司、依维莫司、替西罗莫司和他克莫司。因此，进一步研究 mTOR 抑制剂治疗 SARS-CoV-2 感染或 COVID-19 是非常值得的。
