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高渗盐溶液对严重急性呼吸综合征冠状病毒2在肺和肾上皮细胞中复制的抑制作用

Inhibition of Severe Acute Respiratory Syndrome Coronavirus 2 Replication by Hypertonic Saline Solution in Lung and Kidney Epithelial Cells.

作者信息

Machado Rafael R G, Glaser Talita, Araujo Danielle B, Petiz Lyvia Lintzmaier, Oliveira Danielle B L, Durigon Giuliana S, Leal Alessandra L, Pinho João Renato R, Ferreira Luis C S, Ulrich Henning, Durigon Edison L, Guzzo Cristiane Rodrigues

机构信息

Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508, Brazil.

Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo 05508, Brazil.

出版信息

ACS Pharmacol Transl Sci. 2021 Sep 3;4(5):1514-1527. doi: 10.1021/acsptsci.1c00080. eCollection 2021 Oct 8.

Abstract

An unprecedented global health crisis has been caused by a new virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We performed experiments to test if a hypertonic saline solution was capable of inhibiting virus replication. Our data show that 1.2% NaCl inhibited virus replication by 90%, achieving 100% of inhibition at 1.5% in the nonhuman primate kidney cell line Vero, and 1.1% of NaCl was sufficient to inhibit the virus replication by 88% in human epithelial lung cell line Calu-3. Furthermore, our results indicate that the inhibition is due to an intracellular mechanism and not to the dissociation of the spike SARS-CoV-2 protein and its human receptor. NaCl depolarizes the plasma membrane causing a low energy state (high ADP/ATP concentration ratio) without impairing mitochondrial function, supposedly associated with the inhibition of the SARS-CoV-2 life cycle. Membrane depolarization and intracellular energy deprivation are possible mechanisms by which the hypertonic saline solution efficiently prevents virus replication assays.

摘要

一种名为严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的新型病毒引发了一场前所未有的全球健康危机。我们进行了实验,以测试高渗盐溶液是否能够抑制病毒复制。我们的数据表明,1.2%的氯化钠可将病毒复制抑制90%,在非人类灵长类动物肾细胞系Vero中,1.5%的氯化钠可实现100%的抑制效果,而1.1%的氯化钠足以在人肺上皮细胞系Calu-3中将病毒复制抑制88%。此外,我们的结果表明,这种抑制作用是由于细胞内机制,而非SARS-CoV-2刺突蛋白与其人类受体的解离。氯化钠使质膜去极化,导致低能量状态(高ADP/ATP浓度比),而不会损害线粒体功能,推测这与抑制SARS-CoV-2生命周期有关。膜去极化和细胞内能量剥夺可能是高渗盐溶液有效阻止病毒复制试验的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f6f/8506614/9839902b7900/pt1c00080_0001.jpg

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