| COVID-19 is highly contagious and quickly spread to all 34 provinces in China within a month.In order to control the COVID-19 epidemic,China implemented strict control measures,and the epidemic has been effectively alleviated.But COVID-19 is spreading rapidly around the world.On March 11,the World Health Organization(WHO)declared the disease a global pandemic.The number of infected patients and epidemic area of SARS-Co V-2 have far exceeded SARS and MERS.As of 4:31 PM on March 8,2020,the cumulative number of COVID-19 patients worldwide had exceeded440 million,with 6,004,421 deaths.COVID-19 poses a serious threat to global public health,and with it the way we live will change dramatically.Although we have gained some experience with COVID-19 treatments,the results of the WHO’s Solidarity Trial in December 2020 indicated that remdesivir,hydroxychloroquine,lopinavir/ritonavir,and interferon had little or no effect on 28-day mortality in hospitalized patients.In addition,the use of convalescent plasma,intravenous injection of COVID-19 human immunoglobulin,tocilizumab and other immunotherapy is relatively expensive.The WHO says scientists around the world are working to find and develop treatments for COVID-19.Therefore,finding and developing effective and affordable treatments for COVID-19 is one of the important research directions.Proteomics can comprehensively understand the processes of disease occurrence and cell metabolism at the protein level.Proteomics based on the overall level of proteins plays an important role in human disease research.Applications of proteomics can better understand disease processes,develop biomarkers for early diagnosis of disease,and accelerate drug development.Urine samples have the advantages of being non-invasive,easy to obtain,and can be continuously collected.There are many proteins in urine,which can reflect changes in human physiology and pathology.Therefore,this study explored signaling pathways and therapeutic options based on urine proteome in COVID-19.First,urine proteomes from 86 patients with COVID-19,55 patients with common pneumonia,and 176 healthy controls were compared and analyzed,and it was found that proteins related to immune and metabolic were significantly altered in patients with COVID-19.An antiviral immune response pathway was then found to be activated in the urine of COVID-19 patients,and proteins associated with this pathway were significantly overexpressed,including the receptor DDX58/RIG-I that recognizes viral ds RNA,the virus-response-specific transcription factor STAT1,and a variety of interferon-stimulating genes(ISGs).These suggest that urine can reflect changes in the body.Further analysis revealed that a protein,CLYBL,which is not currently included in the common database of bioinformatics annotations,is only highly expressed in the urine of COVID-19 patients.CLYBL is a citramalyl-Co A lyase that converts itaconate to acetyl-Co A.The high expression of CLYBL may be a key factor leading to the depletion of itaconate,an anti-inflammatory metabolite.Itaconate plays an important role in cell protection such as anti-oxidation and anti-inflammation,so it is speculated that supplementing itaconate and inhibiting CLYBL may be the treatment for COVID-19.In addition,the urine proteomes of severe and moderate patients in the early stages of COVID-19 were compared to find biomarkers that predict the onset of severe COVID-19.The biological function of these proteins suggests that macrophage-induced inflammatory response and thrombolysis may play a key role in disease progression.In conclusion,current studies suggest that urine,as a non-invasive,easily accessible and continuously collected biological sample,can reflect some changes occurring in the human body,and can also be used to find biomarkers and potential therapeutic targets.Supplementing itaconate and inhibiting CLYBL may be the potential therapeutic approaches for COVID-19. |
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