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雪貂模型中SARS-CoV-2感染的时间序列代谢组学分析

A Time-Series Metabolomic Analysis of SARS-CoV-2 Infection in a Ferret Model.

作者信息

Karpe Avinash V, Nguyen Thao V, Shah Rohan M, Au Gough G, McAuley Alexander J, Marsh Glenn A, Riddell Sarah, Vasan Seshadri S, Beale David J

机构信息

Land and Water, Commonwealth Scientific and Industrial Research Organisation, Ecosciences Precinct, Dutton Park, QLD 4102, Australia.

Department of Chemistry and Biotechnology, School of Science, Computing and Engineering Technologies, Swinburne University of Technology, Hawthorn, VIC 3122, Australia.

出版信息

Metabolites. 2022 Nov 21;12(11):1151. doi: 10.3390/metabo12111151.

Abstract

The global threat of COVID-19 has led to an increased use of metabolomics to study SARS-CoV-2 infections in animals and humans. In spite of these efforts, however, understanding the metabolome of SARS-CoV-2 during an infection remains difficult and incomplete. In this study, metabolic responses to a SAS-CoV-2 challenge experiment were studied in nasal washes collected from an asymptomatic ferret model ( = 20) at different time points before and after infection using an LC-MS-based metabolomics approach. A multivariate analysis of the nasal wash metabolome data revealed several statistically significant features. Despite no effects of sex or interaction between sex and time on the time course of SARS-CoV-2 infection, 16 metabolites were significantly different at all time points post-infection. Among these altered metabolites, the relative abundance of taurine was elevated post-infection, which could be an indication of hepatotoxicity, while the accumulation of sialic acids could indicate SARS-CoV-2 invasion. Enrichment analysis identified several pathways influenced by SARS-CoV-2 infection. Of these, sugar, glycan, and amino acid metabolisms were the key altered pathways in the upper respiratory channel during infection. These findings provide some new insights into the progression of SARS-CoV-2 infection in ferrets at the metabolic level, which could be useful for the development of early clinical diagnosis tools and new or repurposed drug therapies.

摘要

新冠病毒(COVID-19)的全球威胁导致代谢组学在研究动物和人类的新冠病毒感染方面的应用增加。然而,尽管做出了这些努力,了解新冠病毒感染期间的代谢组仍然困难且不完整。在本研究中,使用基于液相色谱-质谱联用(LC-MS)的代谢组学方法,对从无症状雪貂模型(n = 20)在感染前后不同时间点收集的鼻腔灌洗液中对新冠病毒攻击实验的代谢反应进行了研究。对鼻腔灌洗液代谢组数据的多变量分析揭示了几个具有统计学意义的特征。尽管性别或性别与时间之间的相互作用对新冠病毒感染的时间进程没有影响,但在感染后的所有时间点,有16种代谢物存在显著差异。在这些变化的代谢物中,感染后牛磺酸的相对丰度升高,这可能表明肝毒性,而唾液酸的积累可能表明新冠病毒的入侵。富集分析确定了受新冠病毒感染影响的几个途径。其中,糖、聚糖和氨基酸代谢是感染期间上呼吸道中关键的变化途径。这些发现为雪貂体内新冠病毒感染在代谢水平上的进展提供了一些新见解,这可能有助于开发早期临床诊断工具以及新的或重新利用的药物疗法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ffd/9699618/7605b59ce859/metabolites-12-01151-g001.jpg

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