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内质网作为新冠病毒感染管理的潜在治疗靶点?

Endoplasmic reticulum as a potential therapeutic target for covid-19 infection management?

作者信息

Sureda Antoni, Alizadeh Javad, Nabavi Seyed Fazel, Berindan-Neagoe Ioana, Cismaru Cosmin Andrei, Jeandet Philippe, Łos Marek J, Clementi Emilio, Nabavi Seyed Mohammad, Ghavami Saeid

机构信息

Research Group in Community Nutrition and Oxidative Stress, University of Balearic Islands, Health Research Institute of Balearic Islands (IdISBa), and CIBEROBN (Physiopathology of Obesity and Nutrition), E-07122, Palma, Balearic Islands, Spain.

Department of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, Canada.

出版信息

Eur J Pharmacol. 2020 Sep 5;882:173288. doi: 10.1016/j.ejphar.2020.173288. Epub 2020 Jun 17.

DOI:10.1016/j.ejphar.2020.173288
PMID:32561291
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7297682/
Abstract

In December 2019, many pneumonia cases with unidentified sources appeared in Wuhan, Hubei, China, with clinical symptoms like viral pneumonia. Deep sequencing analysis of samples from lower respiratory tract revealed a novel coronavirus, called 2019 novel coronavirus (2019-nCoV). Currently there is a rapid global spread. World Health Organization declare the disease a pandemic condition. The pathologic source of this disease was a new RNA virus from Coronaviridae family, which was named COVID-19. SARS-CoV-2 entry starts with the binding of the spike glycoprotein expressed on the viral envelope to ACE2 on the alveolar surface followed by clathrin-dependent endocytosis of the SARS-CoV-2 and ACE2 complex. SARS-CoV-2 enters the cells through endocytosis process, which is possibly facilitated, via a pH dependent endosomal cysteine protease cathepsins. Once inside the cells, SARS-CoV-2 exploits the endogenous transcriptional machinery of alveolar cells to replicate and spread through the entire lung. Endosomal acidic pH for SARS-CoV-2 processing and internalization is critical. After entering the cells, it possibly activates or hijack many intracellular pathways in favor of its replication. In the current opinion article, we will explain the possible involvement of unfolded protein response as a cellular stress response to the SARS-CoV-2 infection.

摘要

2019年12月,中国湖北省武汉市出现多例不明原因的肺炎病例,临床症状类似病毒性肺炎。对下呼吸道样本进行的深度测序分析发现了一种新型冠状病毒,名为2019新型冠状病毒(2019-nCoV)。目前该病毒在全球迅速传播。世界卫生组织宣布该疾病为大流行疾病。这种疾病的病原体是一种来自冠状病毒科的新型RNA病毒,被命名为COVID-19。严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的进入始于病毒包膜上表达的刺突糖蛋白与肺泡表面的血管紧张素转换酶2(ACE2)结合,随后SARS-CoV-2与ACE2复合物通过网格蛋白依赖的内吞作用进入细胞。SARS-CoV-2通过内吞作用进入细胞,这一过程可能通过一种pH依赖的内体半胱氨酸蛋白酶组织蛋白酶来促进。一旦进入细胞内,SARS-CoV-2利用肺泡细胞的内源性转录机制进行复制,并在整个肺部传播。内体酸性pH值对于SARS-CoV-2的处理和内化至关重要。进入细胞后,它可能激活或劫持许多细胞内途径以利于其复制。在这篇观点文章中,我们将解释未折叠蛋白反应作为一种细胞应激反应可能参与SARS-CoV-2感染的情况。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3be8/7297682/d6ab9e283a6b/sc1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3be8/7297682/d6ab9e283a6b/sc1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3be8/7297682/d6ab9e283a6b/sc1_lrg.jpg

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