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代谢靶向治疗干预能否成功征服 SARS-CoV-2?一种科学合理性。

Can a metabolism-targeted therapeutic intervention successfully subjugate SARS-COV-2? A scientific rational.

机构信息

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Student Research Committee, Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Biomed Pharmacother. 2020 Nov;131:110694. doi: 10.1016/j.biopha.2020.110694. Epub 2020 Aug 27.

Abstract

As a process entailing a high turnover of the host cell molecules, viral replication is required for a successful viral infection and requests virus capacity to acquire the macromolecules required for its propagation. To this end, viruses have adopted several strategies to harness cellular metabolism in accordance with their specific demands. Most viruses upregulate specific cellular anabolic pathways and are largely dependent on such alterations. RNA viruses, for example, upregulate both glycolysisand glycogenolysis providing TCA cycle intermediates essential for anabolic lipogenesis. Also, these infections usually induce the PPP, leading to increased nucleotide levels supporting viral replication. SARS-CoV-2 (the cause of COVID-19)that has so far spread from China throughout the world is also an RNA virus. Owing to the more metabolic plasticity of uninfected cells, a promising approach for specific antiviral therapy, which has drawn a lot of attention in the recent years, would be the targeting of metabolic changes induced by viruses. In the current review, we first summarize some of virus-induced metabolic adaptations and then based on these information as well as SARS-CoV-2 pathogenesis, propose a potential therapeutic modality for this calamitous world-spreading virus with the hope of employing this strategy for near-future clinical application.

摘要

作为一个涉及宿主细胞分子高周转率的过程,病毒复制是成功病毒感染所必需的,这要求病毒有能力获取其繁殖所需的大分子。为此,病毒采用了几种策略来根据其特定需求利用细胞代谢。大多数病毒上调特定的细胞合成代谢途径,并在很大程度上依赖于这种改变。例如,RNA 病毒上调糖酵解和糖原分解,为合成代谢脂肪生成提供三羧酸 (TCA) 循环中间产物。此外,这些感染通常会诱导 PPP,导致核苷酸水平升高,从而支持病毒复制。迄今为止,已从中国传播到世界各地的 SARS-CoV-2(COVID-19 的病因)也是一种 RNA 病毒。由于未感染细胞的代谢可塑性更高,因此针对病毒诱导的代谢变化的特定抗病毒治疗方法成为一种有前途的方法,近年来引起了广泛关注。在本综述中,我们首先总结了一些病毒诱导的代谢适应,然后基于这些信息以及 SARS-CoV-2 的发病机制,为这种灾难性的世界传播病毒提出一种潜在的治疗模式,希望将该策略用于不久的将来的临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e961/7451059/5175c9f555e4/ga1_lrg.jpg

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