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mTOR 激酶是呼吸道合胞病毒和冠状病毒的治疗靶点。

mTOR kinase is a therapeutic target for respiratory syncytial virus and coronaviruses.

机构信息

Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.

Department of Research Administration Children's Medical Center, Dallas, TX, 75235, USA.

出版信息

Sci Rep. 2021 Dec 24;11(1):24442. doi: 10.1038/s41598-021-03814-7.

Abstract

Therapeutic interventions targeting viral infections remain a significant challenge for both the medical and scientific communities. While specific antiviral agents have shown success as therapeutics, viral resistance inevitably develops, making many of these approaches ineffective. This inescapable obstacle warrants alternative approaches, such as the targeting of host cellular factors. Respiratory syncytial virus (RSV), the major respiratory pathogen of infants and children worldwide, causes respiratory tract infection ranging from mild upper respiratory tract symptoms to severe life-threatening lower respiratory tract disease. Despite the fact that the molecular biology of the virus, which was originally discovered in 1956, is well described, there is no vaccine or effective antiviral treatment against RSV infection. Here, we demonstrate that targeting host factors, specifically, mTOR signaling, reduces RSV protein production and generation of infectious progeny virus. Further, we show that this approach can be generalizable as inhibition of mTOR kinases reduces coronavirus gene expression, mRNA transcription and protein production. Overall, defining virus replication-dependent host functions may be an effective means to combat viral infections, particularly in the absence of antiviral drugs.

摘要

针对病毒感染的治疗干预仍然是医学和科学界的重大挑战。虽然特定的抗病毒药物已被证明是有效的治疗方法,但病毒耐药性不可避免地会出现,使得许多这些方法无效。这种不可避免的障碍需要替代方法,例如针对宿主细胞因子的靶向治疗。呼吸道合胞病毒(RSV)是全球婴儿和儿童的主要呼吸道病原体,引起从轻度上呼吸道症状到严重危及生命的下呼吸道疾病的呼吸道感染。尽管该病毒的分子生物学最初于 1956 年被发现,但目前尚无针对 RSV 感染的疫苗或有效抗病毒治疗方法。在这里,我们证明靶向宿主因子,特别是 mTOR 信号通路,可以减少 RSV 蛋白的产生和传染性子代病毒的产生。此外,我们还表明,这种方法具有普遍性,因为抑制 mTOR 激酶可减少冠状病毒基因表达、mRNA 转录和蛋白产生。总的来说,确定病毒复制依赖性宿主功能可能是对抗病毒感染的有效手段,特别是在没有抗病毒药物的情况下。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8309/8709853/7e262d21ee38/41598_2021_3814_Fig1_HTML.jpg

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