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,...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.展开更多
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)+4 种基金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)Guangdong Provincial Key Laboratory of Research on Emergency in TCM(2017B030314176).
文摘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.
