SARS-CoV-2 and Glutamine: SARS-CoV-2 Triggered Pathogenesis via Metabolic Reprograming of Glutamine in Host Cells.
SARS-CoV-2 and Glutamine: SARS-CoV-2 Triggered Pathogenesis via Metabolic Reprograming of Glutamine in Host Cells.
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DOI：
10.3389/fmolb.2020.627842
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发表时间：
2020
影响因子：
5
通讯作者：
Kang SG
中科院分区：
文献类型：
--
作者：
Bharadwaj S;Singh M;Kirtipal N;Kang SG
严重急性呼吸系统综合征冠状病毒2 （SARS-CoV-2）感染，作为2019年冠状病毒病（COVID-19）大流行，已在全球造成100多万人死亡，研究人员正在不断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和诱导发病机制，我们假设SARS-CoV-2也可能需要增加葡萄糖和谷氨酰胺等合成代谢，以支持其在感染周期中的能量和生物合成需求。近年来，糖代谢异常在SARS-CoV-2发病机制中的作用已得到证实，但谷氨酰胺代谢异常在其感染中的作用尚未被提及。从这个角度来看，我们试图通过与其他病毒感染/癌症代谢的比较，以及现有的临床数据或对SARS-CoV-2发病机制的研究，总结SARS-CoV-2感染后宿主细胞中谷氨酰胺代谢重编程可能发生的生化事件。这一系统性假说总结了谷氨酰胺酶-1 （GLS1）、磷酸丝氨酸转氨酶（PSAT1）、缺氧诱导因子-1α (HIF-1α)、哺乳动物雷帕霉素复合物靶点1 （mTORC1）、谷氨酰胺-果糖氨基转移酶1/2 （GFAT1/2）和转录因子Myc作为介导和促进SARS-CoV-2感染细胞谷氨酰胺代谢重编程的关键细胞因子的重要作用。在缺乏SARS-CoV-2诱导谷氨酰胺代谢重编程的具体数据的情况下，本研究努力将空白与SARS-CoV-2感染与谷氨酰胺代谢改变的现有临床证据联系起来，并希望通过体外或体内方法的阐明，有助于设计治疗开发的策略方法。
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 in vitro or in vivo approaches.
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