机构：[1]The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China广东省中医院[2]State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China[3]Beijing Pineal Health Management Co. Ltd, Beijing 102206, China[4]Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou 510060, China[5]The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China[6]Guangzhou Institute of Respiratory Disease, Guangzhou 510120, China[7]Guangdong Provincial Key Laboratory of Research on Emergency in TCM, Guangzhou 510120, China[8]Joint Center for Translational Medicine, Tianjin Medical University Baodi Clinical College, Tianjin 301800, China
Signaling pathway alterations in COVID-19 of living humans as well as therapeutic targets of the host proteins are not clear. We analyzed 317 urine proteomes, including 86 COVID-19, 55 pneumonia and 176 healthy controls, and identified specific RNA virus detector protein DDX58/RIG-I only in COVID-19 samples. Comparison of the COVID-19 urinary proteomes with controls revealed major pathway alterations in immunity, metabolism and protein localization. Biomarkers that may stratify severe symptoms from moderate ones suggested that macrophage induced inflammation and thrombolysis may play a critical role in worsening the disease. Hyper activation of the TCA cycle is evident and a macrophage enriched enzyme CLYBL is up regulated in COVID-19 patients. As CLYBL converts the immune modulatory TCA cycle metabolite itaconate through the citramalyl-CoA intermediate to acetyl-CoA, an increase in CLYBL may lead to the depletion of itaconate, limiting its anti-inflammatory function. These observations suggest that supplementation of itaconate and inhibition of CLYBL are possible therapeutic options for treating COVID-19, opening an avenue of modulating host defense as a means of combating SARS-CoV-2 viruses.
基金：
This work was supported by the National Key Research
and Development Program of China (2017YFA0505102,
2017YFA0505103, 2017YFA0505104, 2017YFC0908404,
2018YFA0507503, 2020YFA0708001), the National Natural Science
Foundation of China (81874237, 31870828), Major National Science and
technology projects (2017ZX10305501-006), National Administration of
Traditional Chinese Medicine: 2019 Project of Building Evidence Based
Practice Capacity for TCM (2019XZZX-LG003), Guangdong Key-Area
Research and Development Program (2019B020229002,
2020B1111300005), Guangzhou Science and Technology Program
(201902020009), and Guangdong Provincial Key Laboratory of Research
on Emergency in TCM (2017B030314176).
第一作者机构：[1]The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China[7]Guangdong Provincial Key Laboratory of Research on Emergency in TCM, Guangzhou 510120, China
共同第一作者：
通讯作者：
通讯机构：[1]The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China[7]Guangdong Provincial Key Laboratory of Research on Emergency in TCM, Guangzhou 510120, China
推荐引用方式(GB/T 7714)：
Liu Yuntao,Song Lan,Zheng Nairen,et al.A urinary proteomic landscape of COVID-19 progression identifies signaling pathways and therapeutic options[J].SCIENCE CHINA-LIFE SCIENCES.2022,65(9):1866-1880.doi:10.1007/s11427-021-2070-y.
生物学