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严重急性呼吸综合征冠状病毒2与谷氨酰胺:严重急性呼吸综合征冠状病毒2引发的发病机制——宿主细胞中谷氨酰胺的代谢重编程

SARS-CoV-2 and Glutamine: SARS-CoV-2 Triggered Pathogenesis Metabolic Reprograming of Glutamine in Host Cells.

作者信息

Bharadwaj Shiv, Singh Mahendra, Kirtipal Nikhil, Kang Sang Gu

机构信息

Department of Biotechnology, Institute of Biotechnology, College of Life and Applied Sciences, Yeungnam University, Gyeongsan, South Korea.

Department of Science, Modern Institute of Technology, Rishikesh, India.

出版信息

Front Mol Biosci. 2021 Jan 11;7:627842. doi: 10.3389/fmolb.2020.627842. eCollection 2020.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as coronavirus disease 2019 (COVID-19) pandemic, has killed more than a million people worldwide, and researchers are constantly working to develop therapeutics in the treatment and prevention of this new viral infection. To infect and induced pathogenesis as observed in other viral infections, we postulated that SARS-CoV-2 may also require an escalation in the anabolic metabolism, such as glucose and glutamine, to support its energy and biosynthetic requirements during the infection cycle. Recently, the requirement of altered glucose metabolism in SARS-CoV-2 pathogenesis was demonstrated, but the role of dysregulated glutamine metabolism is not yet mentioned for its infection. In this perspective, we have attempted to provide a summary of possible biochemical events on putative metabolic reprograming of glutamine in host cells upon SARS-CoV-2 infection by comparison to other viral infections/cancer metabolism and available clinical data or research on SARS-CoV-2 pathogenesis. This systematic hypothesis concluded the vital role of glutaminase-1 (GLS1), phosphoserine aminotransferase (PSAT1), hypoxia-inducible factor-1 alpha (HIF-1α), mammalian target of rapamycin complex 1 (mTORC1), glutamine-fructose amidotransferase 1/2 (GFAT1/2), and transcription factor Myc as key cellular factors to mediate and promote the glutamine metabolic reprogramming in SARS-CoV-2 infected cells. In absence of concrete data available for SARS-CoV-2 induced metabolic reprogramming of glutamine, this study efforts to connect the gaps with available clinical shreds of evidence in SARS-CoV-2 infection with altered glutamine metabolism and hopefully could be beneficial in the designing of strategic methods for therapeutic development with elucidation using or approaches.

摘要

严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染,即2019冠状病毒病(COVID-19)大流行,已在全球造成超过100万人死亡,研究人员一直在努力开发治疗和预防这种新型病毒感染的疗法。为了像在其他病毒感染中观察到的那样感染并引发发病机制,我们推测SARS-CoV-2在感染周期中可能也需要增强合成代谢,如葡萄糖和谷氨酰胺代谢,以满足其能量和生物合成需求。最近,已证明SARS-CoV-2发病机制中存在葡萄糖代谢改变的需求,但谷氨酰胺代谢失调在其感染中的作用尚未提及。从这个角度来看,我们试图通过与其他病毒感染/癌症代谢以及关于SARS-CoV-2发病机制的现有临床数据或研究进行比较,总结SARS-CoV-2感染后宿主细胞中谷氨酰胺假定代谢重编程可能的生化事件。这一系统性假设得出结论,谷氨酰胺酶-1(GLS1)、磷酸丝氨酸转氨酶(PSAT1)、缺氧诱导因子-1α(HIF-1α)、哺乳动物雷帕霉素靶蛋白复合物1(mTORC1)、谷氨酰胺-果糖酰胺转移酶1/2(GFAT1/2)和转录因子Myc作为关键细胞因子,介导并促进SARS-CoV-2感染细胞中的谷氨酰胺代谢重编程。由于缺乏SARS-CoV-2诱导的谷氨酰胺代谢重编程的具体数据,本研究努力将SARS-CoV-2感染中谷氨酰胺代谢改变的现有临床证据缺口联系起来,有望有助于设计治疗开发的战略方法,并通过 或 方法进行阐明。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d01/7873863/a8c2a90246e8/fmolb-07-627842-g0001.jpg

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